Viruses are the most abundant obligate intracellular entities in our body. Until recently, they were only considered to be pathogens that caused a broad array of pathologies, ranging from mild disease to deaths in the most severe cases. However, recent advances in unbiased mass sequencing techniques as well as increasing epidemiological evidence have indicated that the human body is home to diverse viral species under non-pathological conditions. Despite these studies, the description of the presumably healthy viral flora, i.e. the normal human virome, is still in its infancy regarding viral composition and dynamics. This review summarizes our current knowledge of the human virome under non-pathological conditions.

Since their discovery more than 100 years ago, viruses have been commonly described as obligate intracellular pathogens. Historically, the first studied virus was the one causing rabies, by Louis Pasteur. However, it was the Russian biologist, Dmitri Ivanovsky, and the Dutch botanist, Martinus Willem Beijerinckwent, who first isolated a tobacco-infecting microbe that caused tobacco mosaic disease. Ivanovsky demonstrated that crushed, infected tobacco leaf extracts remained infectious even after Chamberland filtration, which normally retains bacteria. He suggested that the infection might be caused by a bacterial toxin. However, Beijerinck went one step further, concluding that this new pathogen required living plants to replicate and multiply [1]. Subsequent studies showed that viruses infect all domains of life, including bacteria, archaea and eukaryotes, and are found in all ecological niches [2]. This pleiotropic distribution on our planet allows viruses to play the role of ‘natural motors' that drive global energy and nutrient cycling [3,4]. Until very recently, human viruses were considered only pathogens that were capable of causing human pandemics and a wide range of diseases that in some cases lead to a fatal outcome. With the development of new sequencing technologies (see the following section), which have allowed the analysis of the global viral population (DNA and RNA) in humans, known as the human virome, completely new human-associated viruses have emerged [5,6]. However, the majority of these high-throughput sequencing techniques were performed with the use of filters with pore sizes in the range of 0.2-0.45 μm, which filter larger viruses (see the section entitled ‘The human megavirome'), resulting in a technical bias of the human virome. In this context, it became rapidly clear that viral richness and diversity in the human body under non-pathological conditions were widely underestimated. As an example, a rough estimation based on bacteria-infecting viruses (bacteriophages) indicates that there are 100 times more viruses than eukaryotic cells in our body [2,7]. Human-associated viruses control the microbial diversity of the human gut and skin [8,9]. Viruses affect the very foundation of our nature, our genome. Reminiscences of ancestral human-viral cohabitation are imprinted in our genome with approximately 100,000 known endogenous viral fragments, representing approximately 8% of our genome [10]. Finally, endogenous viral proteins have been associated with important physiological functions, such as mammal placental morphogenesis [11,12].

In the present review, we briefly present the evolution of the virological techniques employed in the discovery of human-associated viruses. We then explore existing knowledge of the viral diversity found in human physiological systems under non-pathological conditions. Finally, we discuss the consequences of this human-virus cohabitation.

Describing the human viral flora requires the right molecular and cellular tools. Historically, classical virology techniques were based on viral isolation from cells and the subsequent observation of cytopathic effects on cell lines or the intracerebral inoculation of suckling mice. Immunological methods, such as seroneutralization or hemagglutination, were then used to detect viral antigens. These techniques were largely used for the isolation of new pathogenic viruses that could be cultivated [13]. With progress in the field of molecular biology, PCR-based methods became the main techniques for viral detection from diverse environmental and clinical samples [14]. However, the identification of new or highly divergent viruses that could not be cultivated remained challenging. The development of next-generation sequencing techniques made it possible to sequence all viral genomes in a given sample without previous assumptions about their nature. These techniques, known as viral metagenomics, allowed the discovery of completely new viral species. Currently, the majority of viral metagenomics studies have been performed with DNA viruses [15,16,17]. To our knowledge, the overrepresentation of metagenomic studies performed on DNA viruses compared with RNA viruses is mainly due to technical limitations [18]. In the near future, advances in methodology will certainly enable routine implementation of RNA viral metagenomics studies in humans.

Digestive Tract

The most extensively studied part of the human body with respect to normal viral communities is the human gastrointestinal tract. The study of this system provides several practical advantages; it represents a non-invasive and easy sampling site as well as provides a sufficient amount of material, thereby allowing for the analysis of the viral composition and dynamics in the gut during a normal life. The first large-scale survey of the human gut virome was performed by Rohwer and colleagues [17] 10 years ago. Using partial shotgun sequencing on viral isolates obtained from healthy feces, they detected the presence of bacteriophages that were mainly related to the Siphoviridae family with an estimated 1,200 genotypes. Interestingly, the majority of detected sequences were unclassified, suggesting that the human gut virome was far more complex than expected. The same group undertook a more detailed study of the composition of DNA viruses from the feces of a healthy 1-week-old infant [19]. The results revealed a viral community with extremely low diversity, with an estimated 8 viral genomes corresponding to Podo-, Sipho- and Myo-virus DNA phages. Interestingly, the overall viral community in the human gut proved to be highly dynamic, changing dramatically between 1 and 2 weeks of age. A more detailed analysis of the infant gut was undertaken by Gordon et al. [16], who performed a comparative study of the viruses present in the fecal microbiota of monozygotic twins and their mothers. Interestingly, they found a high prevalence (>75%) of eukaryotic viral genomes in the gut virome, consisting of sequences related to Herpesviridae, Tymoviridae, Reoviridae and Poxviridae. The majority of bacteriophages and prophages were double-stranded DNA (dsDNA) phages and mostly members of the order Caudovirales. Notably, interindividual viral composition was highly divergent between monozygotic twins, whereas the intraindividual viral flora varied little over a year. All studies agreed that phage communities in the human gut played a critical role in the control of the bacterial population. However, deciphering the phage-bacteria-human interactome has only recently begun to emerge. For instance, the viral metagenomics analysis of the oral cavity of healthy individuals performed by Willner et al. [20] showed that phages represent an important reservoir for bacterial virulence genes; thus, phages play a dual role in which they control the bacterial population but also contribute to bacterial pathogenicity and resistance via horizontal gene transfer.

A continually increasing number of eukaryotic single-stranded DNA (ssDNA) viruses in healthy human stool samples has also been identified through high-throughput sequencing or by PCR-based methods [21]. Interesting examples of ssDNA viruses are those from the Circoviridae family. For example, Li et al. [22] found new cycloviruses and circoviruses in human stool samples from Pakistan, Nigeria, Tunisia, and the USA. Another gyrovirus, the Chicken anemia virus, which is an important avian pathogen, was found with a high prevalence (25%) in the feces of Chilean children, suggesting a possible cross-species transmission from farm animals to humans [22,23,24].

Persistent viral shedding of dsDNA viruses of the Polyomaviridae family from the gastrointestinal tract has been reported in several studies. PCR-based detection of the BK, JC and SV40 viruses were identified in healthy children and adults. Viral detection was more frequent in stool samples from children compared with adults. These findings support the hypothesis that the gastrointestinal tract may be a site of Polyomavirus persistence with a possible fecal-oral route of viral transmission [25].

Multiple RNA viruses, generally considered as human pathogens, have also been detected in the normal gut viral flora. PCR-based or metagenomic analyses on ‘healthy' human feces revealed the presence of several eukaryotic viral families, such as Astroviridae [26,27], Caliciviridae [28,29], Picornaviridae, Reoviridae and Picobirnaviridae, as well as plant viral families, such as Virgaviridae. Picornaviridae is the largest (+) ssRNA viral family with more than 12 recognized genera. Viruses belonging to this family have relatively strict host specificity but can infect a wide range of animals, including humans. Cellular tropism ranges from the gut to the central nervous and respiratory systems. In the gut viral flora, Enterovirus (Poliovirus, Echovirus, Coxsackievirus), Kobuvirus (Aichi virus), Parechovirus and Cardiovirus (Saffold virus) [30] have mainly been found, even in a non-pathological context as demonstrated by Kapusinszky [31]. Human Enterovirus type C has also been identified among healthy children [32,33]. Human Cosavirus (for the common stool-associated Picornavirus) and human Salivirus (for the stool Aichi-like virus), which are not yet recognized as new species, have been reported in several studies in stool samples from healthy children [5,34,35,36,37,38]; however, an understanding of their pathogenicity is lacking because they can also be present in cases of gastroenteritis.

Reoviridae and Picobirnaviridae are two dsRNA virus families responsible for gastroenteritis, but both may be present in apparently healthy humans. For example, rotaviruses (Reoviridae, Rotavirus genus) are a major cause of mortality in children under the age of 5 in developing countries, but some genotypes, such as G10P strains, have frequently been associated with asymptomatic neonatal infections in India [39]. The authors reported no significant differences in the sequences obtained from strains infecting symptomatic and asymptomatic neonates, suggesting that host-specific or environmental factors may contribute to the pathogenicity of a virus in a given population. Similar findings concerning Picobirnaviridae were reviewed by Ganesh [40] in 2012. These interesting findings suggest that frequent enteric infections with diverse enteric viruses occur during early childhood and less frequently in adults without clinical symptoms, indicating a change in the virome based on the age and environment of individuals.

Zhang et al. [41] performed the first metagenomic study on the RNA viral community in human feces. They found that the fecal flora was mainly composed of plant-infecting RNA viruses, specifically Pepper mild mottle virus and Tobacco mosaic virus. Plant viruses are generally considered incapable of infecting humans. However, a few studies have reported the presence of plant viral RNA in the human body, including the respiratory system via cigarette use [42] and the gut via contaminated food consumption [43]. Colson et al. [43] noted a higher prevalence of Pepper mild mottle virus in the stools of adults but not children, possibly due to a difference in their diet. In fact, the presence of plant viruses in humans may not represent an infection of the human body but may be due instead to a passive mechanism, such as the ingestion of contaminated food products, suggesting a role of mammals, including humans, as vectors for plant viruses.

The presence of plant viruses in the human gut highlights the fact that the virome may vary between individuals based on diet as demonstrated for bacteria [44]. The virome of the gut may also depend on environmental factors, such as geography, eating habits or ethnic differences, resulting in interindividual variability.


The human blood and derived products represent a constant need for blood transfusions and medical treatment. However, the blood also represents an important viral reservoir, and some viruses may be pathogenic. Thus, describing the viral flora in the blood has direct consequences for public health. An increasing body of evidence argues that in apparently healthy individuals, the blood is not sterile and may contain many viral species. The majority of the ‘normal' blood viral flora is composed of ssDNA viruses of the Anelloviridae family with Torque teno viruses (TTVs) being the most commonly detected. TTVs are small non-enveloped viruses with icosahedral symmetry that have high genetic diversity. Indeed, the first genus of Anelloviridae, Alphatorquevirus, contains 29 TTV species. Initially detected in a Japanese patient with posttransfusion hepatitis [45], TTVs are now considered commensal with a worldwide distribution [46,47,48]. Although replicative forms of TTV DNA have been detected in peripheral blood mononuclear cells [49], viral loads higher than those in the blood have been identified in the bone marrow, lung, spleen and liver [50]. Thus, it is tempting to speculate that the human blood may play a double role in TTV, both in viral replication and viral dissemination. Several studies have proposed that the main routes for TTV spread are via blood transfusion, oral transmission and sexual contact [48,51,52]. Mother-to-child transmission of TTV has also been reported [53]. These multiple routes of dissemination may contribute to the pandemic nature of TTV infection.

Another frequently detected ssDNA virus family is the Parvoviridae family. Parvoviruses are small non-enveloped viruses with icosahedral symmetry and are approximately 18-26 nm in diameter. Human Parvovirus (PARV)4 was originally detected in the plasma of a person at risk for infection with HIV through intravenous drug use [54]. However, frequent detection of PARV4 and PARV5 in the plasma of apparently healthy blood donors as well as in symptomatic individuals has been reported [55]. In some parts of the world, including sub-Saharan Africa, PARV4 seropositivity is frequently detected with high prevalence in the population [56]. Although infections with PARV4 are not accompanied by long-term viremia, viral DNA sequences can likely be detected in tissues for a long time after exposure [57,58,59], thereby encompassing a form of latency or persistence that is shared with other human PARV, e.g. human PARV B19 and adeno-associated viruses [60,61,62].

Eukaryotic dsDNA viruses have also been detected in blood donors. Egli et al. [63] reported the prevalence of the BK and JC polyomaviruses by testing the blood of 400 donors. Interestingly, they found significant differences between the BK and JC viruses with respect to virus-host interaction and epidemiology. Moreover, lymphotropic Polyomavirus and human Bocavirus (HBoV) have also been frequently found in the peripheral blood of immunocompromised and apparently healthy subjects [64,65].

An increasing number of studies have reported the emergence of new retroviral infections in primate hunters in Africa. Viruses from Retroviridae, such as Simian foamy virus, Spumaretrovirus or Human T-lymphotropic virus 3/4, are naturally acquired by apparently healthy individuals in central Africa after hunting and the butchering of infected meat [66,67]. Moreover, zoonotic retroviruses are frequently detected in the blood of research workers in zoos [68,69,70]. Although the viruses are found in apparently healthy individuals, the long-term consequences of these viral infections must be evaluated. Indeed, it is possible that in the case of persons with immune disorders, these viruses may contribute to the development of chronic pathologies.

RNA viruses are also part of the viral flora in the blood, but they are mainly pathogenic, and in such cases they represent the viremic phase of infection. Only a few examples of circulating ‘asymptomatic' RNA viruses have been reported, but their pathogenicity is not understood. Recently, several arthropod-borne viruses (arboviruses) belonging to the Flaviviridae family, such as Dengue virus, have been detected in the blood of apparently healthy individuals [71]; however, Dengue virus infections can cause undifferentiated fevers and even deaths in some cases. In 2001, Sonoda and Nakayama [72] described circulating Measles virus in peripheral blood mononuclear cells from healthy children exposed to an environment in which measles was circulating. The Measles virus belongs to the Paramyxoviridae family (Morbilivirus genus) and is a major cause of child death in non-vaccinated populations. The authors found a high prevalence of Measles virus (23.4%) in exposed populations, but no detection of viral RNA was observed in unexposed children, suggesting an asymptomatic circulation of the virus.

Respiratory Tract

The respiratory tract is a major gateway of infections for the human body, mainly due to environmental exposure. We distinguish upper respiratory tract infections, which refer to infections of the nasopharynx, larynx, tonsils, sinuses and ears, from lower respiratory tract infections, which refer to infections of the trachea, bronchi and alveoli. The frequency of symptomatic viral respiratory tract infections is higher in young children compared with adults. Although many viruses are responsible for pathologies of the respiratory system (including human rhinoviruses, hRVs, respiratory syncytial virus, influenza and coronaviruses), a number of viruses may be found without any pathological context. In 2009, Willner et al. [73] compared the DNA virome of the upper respiratory tract in people with or without cystic fibrosis to determine whether there was a core respiratory tract virome in non-diseased individuals. In comparison with other viromes, the authors found that the respiratory tract virome had low species richness, most likely due to physical and biological barriers. Although more than 90% of the sequences were unknown, the authors reported the presence of a core set of 19 bacteriophage genomes in the sputum of healthy individuals, reflecting the airborne contamination of each individual. For example, Streptococcus phage Cp-1, Haemophilus influenza phage HP-1 and Brucella melitensis 16 M BrucI prophage were detected along with a random distribution of other phage genotypes. The composition of this phage community may reflect a specific environment, and we can assume that interindividual variability may be due to a difference in environmental exposure. Indeed, some organs, such as the respiratory tract, having frequent contact with the environment, are exposed to different viral communities. In contrast, in cystic fibrosis metagenomes, the pathology appears to favor a phage composition. The study revealed the presence of a core of 20 eukaryotic DNA viral genomes in healthy individuals, mainly composed of adenoviruses, herpesviruses and human papillomaviruses (HPVs). The authors suggested that eukaryotic viral communities in apparently healthy individuals likely represent transient infections that are rapidly cleared by immune cells or viral particles that are removed from the airway via mucociliary clearance.

A metagenomic study conducted in 2012 by Wylie et al. [74] on young children with or without unexplained fever revealed the presence of DNA viruses, including human Parvoviridae viruses (Dependovirus and Bocavirus genera), in the nasal swabs of healthy children. HBoV is the fourth most common virus found in respiratory samples and may be found in healthy subjects [75], but at a lower frequency than it is found in diseases. HBoV may persist in the respiratory tract for a longer period of time than other respiratory agents, resulting in detection of low levels of HBoV [6]. The role of HBoV as a pathogen remains unclear, but the replication mode of this virus, i.e. with the need of ‘helper viruses' (e.g. adenoviruses or herpesviruses), may associate it with respiratory tract diseases [76]. In their metagenomic study, Wylie et al. [74] reported the presence of human adenoviruses in the nasal swabs of healthy children. Adenoviridae (Mastadenovirus genus) viruses are classified into 7 subgroups (A-G) with 55 known serotypes. These viruses usually cause asymptomatic or mild disease in humans, but occasionally some specific subtypes (mainly types 3 and 7) cause severe syndromes, including neurological disorders or deaths in immunocompromised populations or children. In 2011, Heydari et al. [77] reported a case of fatal infection due to the combination of HBoV and human Adenovirus in a previously healthy child. Although a single infection by one of these 2 viruses mainly remains asymptomatic, coinfection with both HBoV and human Adenovirus may result in lethal disease, suggesting that interactions between viruses of the viral communities can lead to pathology.

hRVs are small, non-enveloped, positive ssRNA viruses belonging to the Picornaviridae family (Enterovirus genus). They comprise 3 major genotypes (hRV-A, B and C) that cause a wide range of respiratory illnesses, from mild common colds to serious lower respiratory tract infections [76]. hRVs are also frequently found in asymptomatic children and adults. In 2006, Winther et al. [78] conducted a prospective cohort study of 15 children aged 1-9 years over a 9- to 12-month period. They found a high hRV presence (21%) in the nasal swabs of young children without any reported symptoms. Viral shedding began several days prior to the onset of symptoms and several days after symptoms occurred. They also noted that the maximum duration of viral presence was relatively short (1-3 weeks). Longer hRV presence may be due to reinfection with a new hRV genotype as reported by Van der Zalm et al. [79]. In 2012, Annamalay et al. [80] conducted a similar study on a prospective cohort of 95 children in Australia. No significant difference was observed in the hRV-A prevalence among children with or without symptoms (i.e. a blocked or runny nose).

Wylie et al. [74] revealed the presence of paramyxoviruses (e.g. Paramyxoviridae, Respirovirus and Pneumovirus genera) in the nasal swabs of apparently healthy individuals. They also reported the presence of InfluenzavirusA, Parechovirus and Coronavirus in nasopharyngeal swabs, similar to that reported by Van der Bergh et al. [81]. Wylie et al. [74] reported a difference in the abundance of viral sequences with febrile children exhibiting 1.5-fold more viral sequences than samples from afebrile children. They also reported a difference in the diversity of the viral genera present in the samples with a lower diversity found in apparently healthy children. However, no causal relationship between a specific virus and the pathology was found. These observations support the hypothesis that pathology may be due to an imbalance of the microbial communities present in the human body.

Due to the non-invasive nature of the sampling, mainly viromes of the upper respiratory tract of apparently healthy people have been assessed. The viral composition of the lower respiratory tract has been studied using bronchoalveolar lavage samples. One recent study on bronchoalveolar lavage samples from intensive care unit patients identified the presence of viruses from Herpesviridae, Paramyxoviridae and Picornaviridae families [82]. Notably, these viruses were found not only in pneumonia patients, but also in control subjects without pneumonia illness. Thus, additional studies are needed to assess the viral composition of this part of the respiratory system.


The human teguments comprise the skin, hair and nails, and play a major role as a barrier protecting the human body from the outside environment. They also represent a complex ecosystem harboring diverse bacterial, fungal and viral species. High-throughput sequencing data on the viral flora of the skin have just begun to be generated. Using Illumina technology, Foulongne et al. [15] detected a high diversity of prokaryotic and eukaryotic viral species in DNA extracts from healthy skin swabs. The most abundant were eukaryotic DNA viruses, such as ssDNA viruses of the Circoviridae family as well as dsDNA viruses of the Polyomaviridae and Papillomaviridae families. Members of Circoviridae (Gyrovirus genus) have been previously reported in the human skin of 4% of healthy persons [83]. Sauvage et al. [83] identified a new virus, the human Gyrovirus, in a skin swab sample from an apparently healthy donor. The host range and infection cycle of human Gyrovirus remains unknown. Other ssDNA viruses from the Parvoviridae family were also found in non-diseased human skin. Although initially reported as the etiological agent of erythema infectiosum, PARV B19 is commonly harbored in apparently healthy human skin. Bonvicini et al. [84] found the prevalence of B19 to be 25% in apparently healthy skin biopsies. Interestingly, the group found that young subjects had a significantly higher rate of B19 viremia compared with adults, suggesting that long-term viral persistence may be the common outcome after primary infection.

Polyomaviruses are also common skin viruses. They have a circular dsDNA genome of approximately 5,000 bp that is surrounded by a non-enveloped icosahedral capsid. Polyomaviruses were first described in 1953 in mice, but since then these viruses have been detected in other vertebrate species, including humans. In humans, a new Polyomavirus, Merkel cell Polyomavirus (MCPyV), was recently identified [85,86]. The presence of MCPyV in human skin has been associated with an aggressive form of skin cancer, Merkel cell carcinoma (MCC). MCPyV infections are found in 80% of MCCs. However, MCPyV and two newly identified polyomaviruses, HPyV6 and HPyV7, are also frequently shed from apparently healthy human skin [15,87]. In the case of MCC, the accumulation of deleterious mutations in the MCPyV genome, including the viral T antigen gene, render the virus non-infectious. Thus, the oncogenic role of MCPyV does not necessary reflect its lifestyle but rather the consequence of deleterious viral mutations. Other dsDNA viruses that are associated with neoplastic development have also been identified in healthy skin. Detection of α- and β-HPVs as well as human Herpesvirus (HHV)7 has been reported recently in skin biopsies [88,89]. HHV7 was initially isolated from CD4+ T cells obtained from peripheral blood lymphocytes of an apparently healthy individual [90] and was later associated with primary cutaneous T cell lymphomas (CTCLs). However, the low prevalence of HHV7 in CTCL as well its presence in healthy skin biopsies suggests that HHV7 may not be the primary cause of CTCL [89,91].

Bacteria-infecting viruses are also frequently found in the human skin and most likely play an important role in controlling the bacterial population. Using viral metagenomics, viruses belonging to the Myoviridae, Siphoviridae, Microviridae, Podoviridae and Inoviridae families were identified, and viruses from the Siphoviridae and Microviridae families were the most abundant. One common phage genera present in healthy human skin consisted of bacteriophages infecting Propionibacterium acnes(Siphoviridae family). The P. acnes bacterium represents a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne. Multiple P. acnes bacteriophages isolated from the sebaceous follicles of healthy skin donors have recently been characterized [9]. Interestingly, these phages showed reduced genetic variability with a broad range of infecting bacterial strains, suggesting the existence of evolutionary constraints that preserve the homogeneity of the phage population.

Nervous System

Little information is available concerning the viral flora in the human nervous (central and peripheral) system in apparently healthy conditions. Examples of neurotropic human viruses are the Herpes simplex virus (HSV)1 and HSV2, which belong to the Herpesviridae family. These viruses have a dsDNA genome located within an icosapentahedral capsid surrounded by an amorphous protein-like material (known as the tegument), which is in turn encapsulated by an envelope consisting of polyamines, lipids and glycoproteins [76]. Genetically, HSV1 and HSV2 are closely related, sharing approximately 70% homology. During primary infection, the virus enters the nerve endings at the peripheral mucocutaneous region. The viral capsid is brought via fast axonal transport into the neuronal cell body of the dorsal root ganglia or the trigeminal ganglia. The viral DNA enters the nucleus of the neuron where it enters a latent state [92]. Notably during this period, two latency-associated transcripts are expressed [93]. Latency-associated transcripts have been shown to have antiapoptotic activity, thereby sustaining the survival of neurons. This activity illustrates the virus-to-host adaption and the benefit of a latent persistence in the nervous system. Although HSV1 and HSV2 are associated with clinical complications, the majority of the infections remain asymptomatic for years or even decades. Indeed, under immunocompetent conditions, the reactivated infection usually remains confined to the vicinity of a single dorsal root ganglion. It has been estimated that asymptomatic reactivation of HSV1 may exceed clinical recrudescence, and asymptomatic HSV2 shedding can occur in more than two-thirds of seropositive individuals [94,95].

Another interesting example of a neurotropic virus is the Borna disease virus (BDV), which is part of the Bornaviridae family. BDV is an 80- to 100-nm enveloped virion, containing an 8.9-kb (-) ssRNA genome that replicates in the cell nucleus [96,97]. In vitro BDV induces non-cytopathic chronic infections in neurons [98]. BDV infection was first identified in horses, and natural infections with BDV were subsequently detected in other vertebrates, including humans [99]. In this context, BDV was suggested as a causative agent of diverse human psychiatric disorders [100,101,102]. Despite these findings, the seroprevalence of the virus in healthy control groups makes the causal relationship between BDV infection and brain disorders hardly verifiable [103]. Recently, endogenous BDV sequences homologous to the viral nucleoprotein were detected in several mammalian species, including humans, suggesting an ancient cohabitation with a BDV ancestor [104,105]. Overall, further efforts, especially using a viral metagenomics approach, should be put into the study of the viral diversity of the human nervous system.

Genito-Urinary Tract

The viral flora of the genito-urinary tract has been mainly studied in pathological situations, and gaps in the knowledge of the viral flora in apparently healthy conditions need to be filled. Asymptomatic shedding from the genito-urinary tract was reported mainly for dsDNA eukaryotic viruses of the Adenoviridae, Herpesviridae, Papillomaviridae and Polyomaviridae families with the exception of ssDNA viruses of the Anelloviridae family [83,106,107,108,109,110,111]. In the case of polyomaviruses, it appears that viral excretion was correlated with the host immune status. Indeed, Csoma et al. [112] detected KI virus and WU virus in the urine of renal transplants but not in the control groups. Moreover, immunosuppression due to pregnancy led to a higher prevalence of BK virus in urine samples in pregnant women compared to non-pregnant women [113].

Multiple herpesviruses were also frequently detected in the genito-urinary tract, especially in the semen of apparently healthy donors. In this case it appears that some herpesviruses, such as human Herpesvirus 6 A/B or the Cytomegalovirus, were able to attach to the sperm head with an intact acrosome [108,113]. Thus, given the potential risk some herpesviruses may represent to the newborns, additional research is required to evaluate the impact of this asymptomatic shedding from herpesvirus-positive donor semen.

When examining the repartition of viruses according to their distribution in the human body (fig. 1), one can note that DNA viruses of Herpesviridae, Papillomaviridae, Polyomaviridae and Anelloviridae families are present both in the respiratory tract, the gut, the skin, the blood and the genito-urinary tract. One hypothesis may be related to the viral-host adaptation process. For sustained infection, viruses need to have wide range of body repartition allowing them to proliferate efficiently.

Fig. 1

Description of the viral composition in the human body. Table summarizing the viral families documented (in green) or not documented (in violet) in each human system.

Fig. 1

Description of the viral composition in the human body. Table summarizing the viral families documented (in green) or not documented (in violet) in each human system.

Close modal

Papillomaviruses represent good examples of pleiotropic human viruses in the human body. Papillomaviruses are 55- to 60-nm non-enveloped DNA viruses composed of a single, circular dsDNA molecule. This viral family consists of more than 120 different HPV types, about 40 of which are sexually transmitted HPVs and a dozen have been identified as the causative agents of cervical, anal, vaginal and penile cancer [114]. HPVs are present in more than 99% of cervical cancers, and HPV type 16 (HPV-16) and HPV-18 are the predominant causes of infection in these cases [115]. These two HPV types are indeed associated with 70% of all cervical cancers with predominance of HPV-16 accounting for about 50% of cases [116]. More recently, papillomaviruses were linked to head and neck malignancies as well. In these cases, the primary causes for these carcinomas were attributed to alcohol and tobacco consumption. However, the number of respiratory and digestive tract cancers caused by HPV infections is constantly increasing [117,118,119]. Indeed patients with HPV-positive carcinoma are generally younger adults and not alcohol and tobacco users. These carcinomas are mainly localized in the oropharynx and in particular at the tonsils. HPV is found with a prevalence of 40-90% of the oropharynx cancers, depending on the geographical distribution [120,121,122].

HPVs have cellular tropism for the stratified squamous epithelia. Although the exact mechanism of Papillomavirus tumorigenesis is not fully elucidated it is generally accepted that this effect is mediated through E6, E7 viral proteins which control cell death and proliferation [123,124,125]. Despite the oncogenic properties of these viruses, the majority of HPV infections remain asymptomatic, and they are cleared by most people without medical consequences. Indeed, the clearance of HPV 18 months postinfection in the male population is 100%, whereas in females it is 97%, suggesting that in the case of an immunocompetent host, HPV infection manifests as a transient phenomenon [126,127]. The significance of their presence in an apparently healthy context remains unknown.

dsDNA viruses with large genomes (also known as giant viruses) represent a monophyletic group of viruses classified under the order of Megavirales [128]. Giant viruses are divided into seven viral families, including Poxviridae, Iridoviridae, Ascoviridae, Mimiviridae, Phycodnaviridae, Asfaviridae and the recently described Marseilleviridae [128,129]. These viruses infect a wide range of eukaryotes, including phagocytic protists and humans [130]. In humans, members of only two of the families, Poxviridae and Mimiviridae, have been linked to disease [131,132,133]. With next-generation sequencing technologies, an accumulating body of evidence indicates the presence of these viruses in non-pathological conditions. For instance, a metagenomics study carried out by Willner et al. [73] detected multiple DNA sequences related to Poxviridae, Iridoviridae, Mimiviridae and Phycodnaviridae. Moreover, several studies have identified the presence of giant viruses in the human gut in both adults and babies [16,19,134]. Breitbart et al. [19] detected sequences homologous to Lymphocystis disease virus (Iridoviridae), a fish-infecting pathogen, whereas Gordon et al. [16] detected previously uncharacterized Pox-related viral sequences in the infant gut.

Recently, a new giant virus closely related to Marseilleviridae, Senegalvirus, was recovered from a stool sample of a 20-year-old Senegal man [134]. Senegalvirus was detected by ultradeep sequencing and was isolated using an amoebal coculture. The Senegalvirus dsDNA genome is approximately 373 kbp in length, making this genome the largest among marseilleviruses. In the same stool, sequences related to the giant Mimivirus were also found [135].

Another virus closely related to the Marseilleviridae family was recently identified in human blood. This new virus, Giant Blood Marseillevirus (GBM), has an estimated 357-kbp dsDNA genome surrounded by a 200-nm capsid (fig. 2). The GBM virus was initially isolated from a blood transfusion pocket using a 0.45-µm filter coupled with high-throughput sequencing from a 32-year-old healthy female donor [136]. Further testing identified concomitant elevated IgG levels and viral DNA in some blood donors, suggesting the persistence of the GBM virus in the blood. Interestingly, GBM was found to infect and replicate in human T cells, but not in amoebas.

Fig. 2

Detection of GBM. a Negative staining of a Marseillevirus-like particle (arrow) present in the virus-purified fraction of serum from blood donor No. 27725. b Epifluorescent microscopy images from fluorescent in situ hybridization of GBM in serum from blood donor No. 27725. The DNA probe was synthesized using the Marseillevirus genomic region, orf 152-153, and is marked in green; nuclear staining with DAPI dye is in blue. Scale bar = 10 µm.

Fig. 2

Detection of GBM. a Negative staining of a Marseillevirus-like particle (arrow) present in the virus-purified fraction of serum from blood donor No. 27725. b Epifluorescent microscopy images from fluorescent in situ hybridization of GBM in serum from blood donor No. 27725. The DNA probe was synthesized using the Marseillevirus genomic region, orf 152-153, and is marked in green; nuclear staining with DAPI dye is in blue. Scale bar = 10 µm.

Close modal

In the environment, the majority of Marseillevirus-related viruses have been isolated from aquatic and soil environments, suggesting the possibility of a common infectious route in humans [129,137,138]. Although they are found in non-pathological conditions, the consequences of long-term viral persistence should be further evaluated.

The Human-Virus Interactome Goes Beyond Simple Parasitism

Viruses and humans coexist and are constantly interacting. Historically, viruses have been classified as strict intracellular pathogens. However, with the development of new technologies for viral detection, it has become clear that their presence within the healthy human body goes beyond simple parasitism (fig. 1, 3; table 1). The role of the majority of eukaryotic viruses in the healthy human body remains unclear. Although the long-term consequences of viral presence in terms of pathological conditions should be evaluated, it is possible that such viruses may be considered commensals. In other cases, it is not a single virus that is pathogenic for humans but the coinfection with different viruses. The combination of HBoV and Adenovirus represents a good example of such coinfection [77]. The presence of viruses in the human body without any pathological context could also be beneficial for the body or for the human microbial flora. An example of symbiosis between viruses and the human host is the phage communities of the human gut, and these communities may play an important role in the control of the bacterial population. Conversely, a negative interaction (negative for humans) is that phages may represent an important reservoir for bacterial resistance genes and may contribute to bacterial pathogenicity via horizontal gene transfer [20]. As a result, the boundaries between mutualistic and pathogenic viruses remain elusive and are most likely highly dynamic throughout life [2].

Table 1

Summary of the viral families, genera and, in some cases, species found in each human system

Summary of the viral families, genera and, in some cases, species found in each human system
Summary of the viral families, genera and, in some cases, species found in each human system
Fig. 3

The human virome in non-pathogenic conditions: distribution of the viral families found in the major human systems. Each viral group is represented with a unique color.

Fig. 3

The human virome in non-pathogenic conditions: distribution of the viral families found in the major human systems. Each viral group is represented with a unique color.

Close modal

The human-virus interactome should be considered as a complex web of interactions, defined by multiple factors. These factors can be classified into three categories: virus-specific (e.g. viral genotype, replication mode, host range, abundance), host-specific (e.g. genetic background, age, immune system) and environment-specific (e.g. geographic location, demographic distribution, animal proximity). In the case of the human virome under healthy conditions, the weight of each factor lays at a metastable equilibrium point, allowing viruses and humans to coexist naturally (fig. 4). A change in one of these parameters could lead to the development of disease conditions or the clearance of the virus from the body. From a medical point of view, a new paradigm is thus emerging; if we define an illness as a disruption of the normal ‘healthy' virome, then the restoration of this equilibrium should be the goal of medical treatment, not the elimination of all non-human microorganisms.

Fig. 4

Human virus metastable equilibrium in non-pathogenic conditions. Schematic representation of the steady state of the human virome in non-pathogenic conditions as regulated by three major factors (virus, host and environment). The disequilibrium of this metastable system leads either to viral spreading or to viral clearance.

Fig. 4

Human virus metastable equilibrium in non-pathogenic conditions. Schematic representation of the steady state of the human virome in non-pathogenic conditions as regulated by three major factors (virus, host and environment). The disequilibrium of this metastable system leads either to viral spreading or to viral clearance.

Close modal

This work was supported by the Starting Grant No. 242729 from the European Research Council awarded to C. Desnues.

The authors declare that they have no conflict of interest.

Bos L: Beijerinck's work on tobacco mosaic virus: historical context and legacy. Philos Trans R Soc Lond B Biol Sci 1999;354:675-685.
Haynes M, Rohwer F: The human virome: Metagenomics of the Human Body, 2011, pp 63-77.
Suttle CA: Marine viruses - major players in the global ecosystem. Nat Rev Microbiol 2007;5:801-812.
Fuhrman JA: Marine viruses and their biogeochemical and ecological effects. Nature 1999;399:541-548.
Greninger AL, Runckel C, Chiu CY, Haggerty T, Parsonnet J, Ganem D, DeRisi JL: The complete genome of klassevirus - a novel picornavirus in pediatric stool. Virol J 2009;6:82.
Allander T: Human bocavirus. J Clin Virol 2008;41:29-33.
Weinbauer MG: Ecology of prokaryotic viruses. FEMS Microbiol Rev 2004;28:127-181.
Stern A, Mick E, Tirosh I, Sagy O, Sorek R: CRISPR targeting reveals a reservoir of common phages associated with the human gut microbiome. Genome Res 2012;22:1985-1994.
Marinelli LJ, Fitz-Gibbon S, Hayes C, Bowman C, Inkeles M, Loncaric A, Russell DA, Jacobs-Sera D, Cokus S, Pellegrini M, Kim J, Miller JF, Hatfull GF, Modlin RL: Propionibacterium acnes bacteriophages display limited genetic diversity and broad killing activity against bacterial skin isolates. mBio 2012;3:e00279-12.
Belshaw R, Pereira V, Katzourakis A, Talbot G, Paces J, Burt A, Tristem M: Long-term reinfection of the human genome by endogenous retroviruses. Proc Natl Acad Sci USA 2004;101:4894-4899.
Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S, Keith JC Jr., McCoy JM: Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 2000;403:785-789.
Blaise S, de Parseval N, Benit L, Heidmann T: Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci USA 2003;100:13013-13018.
Specter S: Clinical Virology Manual, ed 2. New York, Elsevier, 1992.
Ratcliff RM, Chang G, Kok T, Sloots TP: Molecular diagnosis of medical viruses. Curr Issues Mol Biol 2007;9:87-102.
Foulongne V, Sauvage V, Hebert C, Dereure O, Cheval J, Gouilh MA, Pariente K, Segondy M, Burguiere A, Manuguerra JC, Caro V, Eloit M: Human skin microbiota: high diversity of DNA viruses identified on the human skin by high throughput sequencing. PloS One 2012;7:e38499.
Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, Rohwer F, Gordon JI: Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 2010;466:334-338.
Breitbart M, Hewson I, Felts B, Mahaffy JM, Nulton J, Salamon P, Rohwer F: Metagenomic analyses of an uncultured viral community from human feces. J Bacteriol 2003;185:6220-6223.
Delwart EL: Viral metagenomics. Rev Med Virol 2007;17:115-131.
Breitbart M, Haynes M, Kelley S, Angly F, Edwards RA, Felts B, Mahaffy JM, Mueller J, Nulton J, Rayhawk S, Rodriguez-Brito B, Salamon P, Rohwer F: Viral diversity and dynamics in an infant gut. Res Microbiol 2008;159:367-373.
Willner D, Furlan M, Schmieder R, Grasis JA, Pride DT, Relman DA, Angly FE, McDole T, Mariella RP Jr, Rohwer F, Haynes M: Metagenomic detection of phage-encoded platelet-binding factors in the human oral cavity. Proc Natl Acad Sci USA 2011;108(suppl 1):4547-4553.
Delwart E, Li L: Rapidly expanding genetic diversity and host range of the circoviridae viral family and other rep encoding small circular ssdna genomes. Virus Res 2012;164:114-121.
Li L, Kapoor A, Slikas B, Bamidele OS, Wang C, Shaukat S, Masroor MA, Wilson ML, Ndjango JB, Peeters M, Gross-Camp ND, Muller MN, Hahn BH, Wolfe ND, Triki H, Bartkus J, Zaidi SZ, Delwart E: Multiple diverse circoviruses infect farm animals and are commonly found in human and chimpanzee feces. J Virol 2010;84:1674-1682.
Phan TG, Li L, O'Ryan MG, Cortes H, Mamani N, Bonkoungou IJ, Wang C, Leutenegger CM, Delwart E: A third gyrovirus species in human faeces. J Gen Virol 2012;93:1356-1361.
Li L, Shan T, Soji OB, Alam MM, Kunz TH, Zaidi SZ, Delwart E: Possible cross-species transmission of circoviruses and cycloviruses among farm animals. J Gen Virol 2011;92:768-772.
Vanchiere JA, Abudayyeh S, Copeland CM, Lu LB, Graham DY, Butel JS: Polyomavirus shedding in the stool of healthy adults. J Clin Microbiol 2009;47:2388-2391.
Gabbay YB, Luz CR, Costa IV, Cavalcante-Pepino EL, Sousa MS, Oliveira KK, Wanzeller AL, Mascarenhas JD, Leite JP, Linhares AC: Prevalence and genetic diversity of astroviruses in children with and without diarrhea in Sao Luis, Maranhao, Brazil. Mem Inst Oswaldo Cruz 2005;100:709-714.
Mendez-Toss M, Griffin DD, Calva J, Contreras JF, Puerto FI, Mota F, Guiscafre H, Cedillo R, Munoz O, Herrera I, Lopez S, Arias CF: Prevalence and genetic diversity of human astroviruses in Mexican children with symptomatic and asymptomatic infections. J Clin Microbiol 2004;42:151-157.
Barreira DM, Ferreira MS, Fumian TM, Checon R, de Sadovsky AD, Leite JP, Miagostovich MP, Spano LC: Viral load and genotypes of noroviruses in symptomatic and asymptomatic children in southeastern Brazil. J Clin Virol 2010;47:60-64.
Ayukekbong J, Lindh M, Nenonen N, Tah F, Nkuo-Akenji T, Bergstrom T: Enteric viruses in healthy children in Cameroon: viral load and genotyping of norovirus strains. J Med Virol 2011;83:2135-2142.
Himeda T, Ohara Y: Saffold virus, a novel human cardiovirus with unknown pathogenicity. J Virol 2012;86:1292-1296.
Kapusinszky B, Minor P, Delwart E: Nearly constant shedding of diverse enteric viruses by two healthy infants. J Clin Microbiol 2012;50:3427-3434.
Sadeuh-Mba SA, Bessaud M, Massenet D, Joffret ML, Endegue MC, Njouom R, Reynes JM, Rousset D, Delpeyroux F: High frequency and diversity of species C enteroviruses in Cameroon and neighboring countries. J Clin Microbiol 2013;51:759-770.
Rakoto-Andrianarivelo M, Guillot S, Iber J, Balanant J, Blondel B, Riquet F, Martin J, Kew O, Randriamanalina B, Razafinimpiasa L, Rousset D, Delpeyroux F: Co-circulation and evolution of polioviruses and species C enteroviruses in a district of Madagascar. PLoS Pathog 2007;3:e191.
Kapoor A, Victoria J, Simmonds P, Slikas E, Chieochansin T, Naeem A, Shaukat S, Sharif S, Alam MM, Angez M, Wang C, Shafer RW, Zaidi S, Delwart E: A highly prevalent and genetically diversified Picornaviridae genus in South Asian children. Proc Natl Acad Sci USA 2008;105:20482-20487.
Dai XQ, Hua XG, Shan TL, Delwart E, Zhao W: Human cosavirus infections in children in China. J Clin Virol 2010;48:228-229.
Li L, Victoria J, Kapoor A, Blinkova O, Wang C, Babrzadeh F, Mason CJ, Pandey P, Triki H, Bahri O, Oderinde BS, Baba MM, Bukbuk DN, Besser JM, Bartkus JM, Delwart EL: A novel picornavirus associated with gastroenteritis. J Virol 2009;83:12002-12006.
Shan T, Wang C, Cui L, Yu Y, Delwart E, Zhao W, Zhu C, Lan D, Dai X, Hua X: Picornavirus salivirus/klassevirus in children with diarrhea, China. Emerg Infect Dis 2010;16:1303-1305.
Stocker A, Souza BF, Ribeiro TC, Netto EM, Araujo LO, Correa JI, Almeida PS, de Mattos AP, Ribeiro Hda C Jr., Pedral-Sampaio DB, Drosten C, Drexler JF: Cosavirus infection in persons with and without gastroenteritis, Brazil. Emerg Infect Dis 2012;18:656-659.
Iturriza Gomara M, Kang G, Mammen A, Jana AK, Abraham M, Desselberger U, Brown D, Gray J: Characterization of G10P[11] rotaviruses causing acute gastroenteritis in neonates and infants in vellore, india. J Clin Microbiol 2004;42:2541-2547.
Ganesh B, Banyai K, Martella V, Jakab F, Masachessi G, Kobayashi N: Picobirnavirus infections: viral persistence and zoonotic potential. Rev Med Virol 2012;22:245-256.
Zhang T, Breitbart M, Lee WH, Run JQ, Wei CL, Soh SW, Hibberd ML, Liu ET, Rohwer F, Ruan Y: RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol 2006;4:e3.
Balique F, Colson P, Raoult D: Tobacco mosaic virus in cigarettes and saliva of smokers. J Clin Virol 2012;55:374-376.
Colson P, Richet H, Desnues C, Balique F, Moal V, Grob JJ, Berbis P, Lecoq H, Harle JR, Berland Y, Raoult D: Pepper mild mottle virus, a plant virus associated with specific immune responses, fever, abdominal pains, and pruritus in humans. PloS One 2010;5:e10041.
Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI: A core gut microbiome in obese and lean twins. Nature 2009;457:480-484.
Nishizawa T, Okamoto H, Konishi K, Yoshizawa H, Miyakawa Y, Mayumi M: A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem Biophys Res Commun 1997;241:92-97.
Virgin HW, Wherry EJ, Ahmed R: Redefining chronic viral infection. Cell 2009;138:30-50.
Breitbart M, Rohwer F: Method for discovering novel DNA viruses in blood using viral particle selection and shotgun sequencing. BioTechniques 2005;39:729-736.
Biagini P, Gallian P, Cantaloube JF, De Micco P, de Lamballerie X: Presence of TT virus in French blood donors and intravenous drug users. J Hepatol 1998;29:684-685.
Okamura A, Yoshioka M, Kubota M, Kikuta H, Ishiko H, Kobayashi K: Detection of a novel DNA virus (TTV) sequence in peripheral blood mononuclear cells. J Med Virol 1999;58:174-177.
Okamoto H, Nishizawa T, Takahashi M, Asabe S, Tsuda F, Yoshikawa A: Heterogeneous distribution of TT virus of distinct genotypes in multiple tissues from infected humans. Virology 2001;288:358-368.
Zheng MY, Lin Y, Li DJ, Ruan HB, Chen Y, Wu TT: TTV and HPV co-infection in cervical smears of patients with cervical lesions in littoral of zhejiang province (in Chinese). Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2010;24:110-112.
Biagini P, Gallian P, Touinssi M, Cantaloube JF, Zapitelli JP, de Lamballerie X, de Micco P: High prevalence of TT virus infection in French blood donors revealed by the use of three PCR systems. Transfusion 2000;40:590-595.
Bagaglio S, Sitia G, Prati D, Cella D, Hasson H, Novati R, Lazzarin A, Morsica G: Mother-to-child transmission of TT virus: sequence analysis of non-coding region of TT virus in infected mother-infant pairs. Arch Virol 2002;147:803-812.
Jones MS, Kapoor A, Lukashov VV, Simmonds P, Hecht F, Delwart E: New DNA viruses identified in patients with acute viral infection syndrome. J Virol 2005;79:8230-8236.
Fryer JF, Delwart E, Hecht FM, Bernardin F, Jones MS, Shah N, Baylis SA: Frequent detection of the parvoviruses, parv4 and parv5, in plasma from blood donors and symptomatic individuals. Transfusion 2007;47:1054-1061.
Sharp CP, LeBreton M, Kantola K, Nana A, Diffo Jle D, Djoko CF, Tamoufe U, Kiyang JA, Babila TG, Ngole EM, Pybus OG, Delwart E, Delaporte E, Peeters M, Soderlund-Venermo M, Hedman K, Wolfe ND, Simmonds P: Widespread infection with homologues of human parvoviruses b19, parv4, and human bocavirus of chimpanzees and gorillas in the wild. J Virol 2010;84:10289-10296.
Longhi E, Bestetti G, Acquaviva V, Foschi A, Piolini R, Meroni L, Magni C, Antinori S, Parravicini C, Corbellino M: Human parvovirus 4 in the bone marrow of Italian patients with aids. AIDS 2007;21:1481-1483.
Manning A, Willey SJ, Bell JE, Simmonds P: Comparison of tissue distribution, persistence, and molecular epidemiology of parvovirus B19 and novel human parvoviruses PARV4 and human bocavirus. J Infect Dis 2007;195:1345-1352.
Schneider B, Fryer JF, Reber U, Fischer HP, Tolba RH, Baylis SA, Eis-Hubinger AM: Persistence of novel human parvovirus PARV4 in liver tissue of adults. J Med Virol 2008;80:345-351.
Isa A, Kasprowicz V, Norbeck O, Loughry A, Jeffery K, Broliden K, Klenerman P, Tolfvenstam T, Bowness P: Prolonged activation of virus-specific CD8+ T cells after acute b19 infection. PLoS Med 2005;2:e343.
Norja P, Hokynar K, Aaltonen LM, Chen R, Ranki A, Partio EK, Kiviluoto O, Davidkin I, Leivo T, Eis-Hubinger AM, Schneider B, Fischer HP, Tolba R, Vapalahti O, Vaheri A, Soderlund-Venermo M, Hedman K: Bioportfolio: lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue. Proc Natl Acad Sci USA 2006;103:7450-7453.
Soderlund-Venermo M, Hokynar K, Nieminen J, Rautakorpi H, Hedman K: Persistence of human parvovirus B19 in human tissues. Pathol Biol 2002;50:307-316.
Egli A, Infanti L, Dumoulin A, Buser A, Samaridis J, Stebler C, Gosert R, Hirsch HH: Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 2009;199:837-846.
Delbue S, Tremolada S, Elia F, Carloni C, Amico S, Tavazzi E, Marchioni E, Novati S, Maserati R, Ferrante P: Lymphotropic polyomavirus is detected in peripheral blood from immunocompromised and healthy subjects. J Clin Virol 2010;47:156-160.
Bonvicini F, Manaresi E, Gentilomi GA, Di Furio F, Zerbini M, Musiani M, Gallinella G: Evidence of human bocavirus viremia in healthy blood donors. Diagn Microbiol Infect Dis 2011;71:460-462.
Wolfe ND, Switzer WM, Carr JK, Bhullar VB, Shanmugam V, Tamoufe U, Prosser AT, Torimiro JN, Wright A, Mpoudi-Ngole E, McCutchan FE, Birx DL, Folks TM, Burke DS, Heneine W: Naturally acquired simian retrovirus infections in central African hunters. Lancet 2004;363:932-937.
Zheng H, Wolfe ND, Sintasath DM, Tamoufe U, Lebreton M, Djoko CF, Diffo Jle D, Pike BL, Heneine W, Switzer WM: Emergence of a novel and highly divergent HTLV-3 in a primate hunter in Cameroon. Virology 2010;401:137-145.
Heneine W, Switzer WM, Sandstrom P, Brown J, Vedapuri S, Schable CA, Khan AS, Lerche NW, Schweizer M, Neumann-Haefelin D, Chapman LE, Folks TM: Identification of a human population infected with simian foamy viruses. Nat Med 1998;4:403-407.
Lerche NW, Switzer WM, Yee JL, Shanmugam V, Rosenthal AN, Chapman LE, Folks TM, Heneine W: Evidence of infection with simian type D retrovirus in persons occupationally exposed to nonhuman primates. J Virol 2001;75:1783-1789.
Sandstrom PA, Phan KO, Switzer WM, Fredeking T, Chapman L, Heneine W, Folks TM: Simian foamy virus infection among zoo keepers. Lancet 2000;355:551-552.
Dias LL, Amarilla AA, Poloni TR, Covas DT, Aquino VH, Figueiredo LT: Detection of dengue virus in sera of Brazilian blood donors. Transfusion 2012;52:1667-1671.
Sonoda S, Nakayama T: Detection of measles virus genome in lymphocytes from asymptomatic healthy children. J Med Virol 2001;65:381-387.
Willner D, Furlan M, Haynes M, Schmieder R, Angly FE, Silva J, Tammadoni S, Nosrat B, Conrad D, Rohwer F: Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals. PloS One 2009;4:e7370.
Wylie KM, Mihindukulasuriya KA, Sodergren E, Weinstock GM, Storch GA: Sequence analysis of the human virome in febrile and afebrile children. PloS One 2012;7:e27735.
Fry AM, Lu X, Chittaganpitch M, Peret T, Fischer J, Dowell SF, Anderson LJ, Erdman D, Olsen SJ: Human bocavirus: a novel parvovirus epidemiologically associated with pneumonia requiring hospitalization in Thailand. J Infect Dis 2007;195:1038-1045.
King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ (eds): Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses. 2011, Academic Press, London.
Heydari H, Mamishi S, Khotaei GT, Moradi S: Fatal type 7 adenovirus associated with human bocavirus infection in a healthy child. J Med Virol 2011;83:1762-1763.
Winther B, Hayden FG, Hendley JO: Picornavirus infections in children diagnosed by RT-PCR during longitudinal surveillance with weekly sampling: association with symptomatic illness and effect of season. J Med Virol 2006;78:644-650.
van der Zalm MM, Wilbrink B, van Ewijk BE, Overduin P, Wolfs TF, van der Ent CK: Highly frequent infections with human rhinovirus in healthy young children: a longitudinal cohort study. J Clin Virol 2011;52:317-320.
Annamalay AA, Khoo SK, Jacoby P, Bizzintino J, Zhang G, Chidlow G, Lee WM, Moore HC, Harnett GB, Smith DW, Gern JE, LeSouef PN, Laing IA, Lehmann D: Prevalence of and risk factors for human rhinovirus infection in healthy aboriginal and non-aboriginal Western Australian children. Pediatr Infect Dis J 2012;31:673-679.
van den Bergh MR, Biesbroek G, Rossen JW, de Steenhuijsen Piters WA, Bosch AA, van Gils EJ, Wang X, Boonacker CW, Veenhoven RH, Bruin JP, Bogaert D, Sanders EA: Associations between pathogens in the upper respiratory tract of young children: interplay between viruses and bacteria. PloS One 2012;7:e47711.
Bousbia S, Papazian L, Saux P, Forel JM, Auffray JP, Martin C, Raoult D, La Scola B: Repertoire of intensive care unit pneumonia microbiota. PloS One 2012;7:e32486.
Sauvage V, Cheval J, Foulongne V, Gouilh MA, Pariente K, Manuguerra JC, Richardson J, Dereure O, Lecuit M, Burguiere A, Caro V, Eloit M: Identification of the first human gyrovirus, a virus related to chicken anemia virus. J Virol 2011;85:7948-7950.
Bonvicini F, La Placa M, Manaresi E, Gallinella G, Gentilomi GA, Zerbini M, Musiani M: Parvovirus B19 DNA is commonly harboured in human skin. Dermatology 2010;220:138-142.
Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human merkel cell carcinoma. Science 2008;319:1096-1100.
Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, Chang Y: T antigen mutations are a human tumor-specific signature for merkel cell polyomavirus. Proc Natl Acad Sci USA 2008;105:16272-16277.
Schowalter RM, Pastrana DV, Pumphrey KA, Moyer AL, Buck CB: Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 2010;7:509-515.
Ruer JB, Pepin L, Gheit T, Vidal C, Kantelip B, Tommasino M, Pretet JL, Mougin C, Aubin F: Detection of alpha- and beta-human papillomavirus (HPV) in cutaneous melanoma: a matched and controlled study using specific multiplex PCR combined with DNA microarray primer extension. Exp Dermatol 2009;18:857-862.
Ponti R, Bergallo M, Costa C, Quaglino P, Fierro MT, Comessatti A, Stroppiana E, Sidoti F, Merlino C, Novelli M, Alotto D, Cavallo R, Bernengo MG: Human herpesvirus 7 detection by quantitative real time polymerase chain reaction in primary cutaneous T cell lymphomas and healthy subjects: lack of a pathogenic role. Br J Dermatol 2008;159:1131-1137.
Frenkel N, Schirmer EC, Wyatt LS, Katsafanas G, Roffman E, Danovich RM, June CH: Isolation of a new herpesvirus from human CD4+ T cells. Proc Natl Acad Sci USA 1990;87:748-752.
Nagore E, Ledesma E, Collado C, Oliver V, Perez-Perez A, Aliaga A: Detection of Epstein-Barr virus and human herpesvirus 7 and 8 genomes in primary cutaneous T and B cell lymphomas. Br J Dermatol 2000;143:320-323.
Steiner I, Kennedy PG: Herpes simplex virus latent infection in the nervous system. J Neurovirol 1995;1:19-29.
Stevens JG, Wagner EK, Devi-Rao GB, Cook ML, Feldman LT: RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science 1987;235:1056-1059.
Knaup B, Schunemann S, Wolff MH: Subclinical reactivation of herpes simplex virus type 1 in the oral cavity. Oral Microbiol Immunol 2000;15:281-283.
Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, Krieger JN, Corey L: Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. New Engl J Med 2000;342:844-850.
Briese T, Schneemann A, Lewis AJ, Park YS, Kim S, Ludwig H, Lipkin WI: Genomic organization of Borna disease virus. Proc Natl Acad Sci USA 1994;91:4362-4366.
Cubitt B, de la Torre JC: Borna disease virus (BDV), a nonsegmented RNA virus, replicates in the nuclei of infected cells where infectious BDV ribonucleoproteins are present. J Virol 1994;68:1371-1381.
Pletnikov MV, Gonzalez-Dunia D, Stitz L: Experimental infection: pathogenesis of neurobehavioral disease; in Carbone KM (ed): Borna Disease Virus and Its Role in Neurobehavioral Disease. Washington, ASM, 2002, pp 125-178.
Kinnunen PM, Palva A, Vaheri A, Vapalahti O: Epidemiology and host spectrum of Borna disease virus infections. J Gen Virol 2013;94:247-262.
Rott R, Herzog S, Fleischer B, Winokur A, Amsterdam J, Dyson W, Koprowski H: Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 1985;228:755-756.
Bode L, Riegel S, Ludwig H, Amsterdam JD, Lange W, Koprowski H: Borna disease virus-specific antibodies in patients with HIV infection and with mental disorders. Lancet 1988;2:689.
Patti AM, Vulcano A, Candelori E, Donfrancesco R, Ludwig H, Bode L: Borna disease virus infection in Italian children: a potential risk for the developing brain? APMIS Suppl 2008:70-73.
Kinnunen PM, Billich C, Ek-Kommonen C, Henttonen H, Kallio RK, Niemimaa J, Palva A, Staeheli P, Vaheri A, Vapalahti O: Serological evidence for Borna disease virus infection in humans, wild rodents and other vertebrates in Finland. J Clin Virol 2007;38:64-69.
Belyi VA, Levine AJ, Skalka AM: Unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes. PLoS Pathog 2010;6:e1001030.
Horie M, Honda T, Suzuki Y, Kobayashi Y, Daito T, Oshida T, Ikuta K, Jern P, Gojobori T, Coffin JM, Tomonaga K: Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature 2010;463:84-87.
Heim A, Ebnet C, Harste G, Pring-Akerblom P: Rapid and quantitative detection of human adenovirus DNA by real-time PCR. J Med Virol 2003;70:228-239.
Zhao Y, Cao X, Zheng Y, Tang J, Cai W, Wang H, Gao Y, Wang Y: Relationship between cervical disease and infection with human papillomavirus types 16 and 18, and herpes simplex virus 1 and 2. J Med Virol 2012;84:1920-1927.
Naumenko VA, Tyulenev YA, Yakovenko SA, Kurilo LF, Shileyko LV, Segal AS, Zavalishina LE, Klimova RR, Tsibizov AS, Alkhovskii SV, Kushch AA: Detection of human cytomegalovirus in motile spermatozoa and spermatogenic cells in testis organotypic culture. Herpesviridae 2011;2:7.
Bialasiewicz S, Whiley DM, Lambert SB, Nissen MD, Sloots TP: Detection of BK, JC, WU, or KI polyomaviruses in faecal, urine, blood, cerebrospinal fluid and respiratory samples. J Clin Virol 2009;45:249-254.
Burian Z, Szabo H, Szekely G, Gyurkovits K, Pankovics P, Farkas T, Reuter G: Detection and follow-up of torque teno midi virus (‘small anelloviruses') in nasopharyngeal aspirates and three other human body fluids in children. Arch Virol 2011;156:1537-1541.
Chan PK, Tam WH, Yeo W, Cheung JL, Zhong S, Cheng AF: High carriage rate of TT virus in the cervices of pregnant women. Clin Infect Dis 2001;32:1376-1377.
Csoma E, Meszaros B, Asztalos L, Konya J, Gergely L: Prevalence of WU and KI polyomaviruses in plasma, urine, and respiratory samples from renal transplant patients. J Med Virol 2011;83:1275-1278.
Kaspersen MD, Larsen PB, Kofod-Olsen E, Fedder J, Bonde J, Hollsberg P: Human herpesvirus-6A/B binds to spermatozoa acrosome and is the most prevalent herpesvirus in semen from sperm donors. PloS One 2012;7:e48810.
Bernard HU, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM: Classification of papillomaviruses (PVS) based on 189 PV types and proposal of taxonomic amendments. Virology 2010;401:70-79.
Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV: The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002;55:244-265.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12-19.
Klein F, Amin Kotb WF, Petersen I: Incidence of human papilloma virus in lung cancer. Lung Cancer 2009;65:13-18.
Ryerson AB, Peters ES, Coughlin SS, Chen VW, Gillison ML, Reichman ME, Wu X, Chaturvedi AK, Kawaoka K: Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003. Cancer 2008;113:2901-2909.
Hansson BG, Rosenquist K, Antonsson A, Wennerberg J, Schildt EB, Bladstrom A, Andersson G: Strong association between infection with human papillomavirus and oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Acta otolaryngol 2005;125:1337-1344.
Hariri S, Unger ER, Sternberg M, Dunne EF, Swan D, Patel S, Markowitz LE: Prevalence of genital human papillomavirus among females in the United States, the national health and nutrition examination survey, 2003-2006. J Infect Dis 2011;204:566-573.
Kreimer AR, Clifford GM, Boyle P, Franceschi S: Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 2005;14:467-475.
St Guily JL, Jacquard AC, Pretet JL, Haesebaert J, Beby-Defaux A, Clavel C, Agius G, Birembaut P, Okais C, Leocmach Y, Soubeyrand B, Pradat P, Riethmuller D, Mougin C, Denis F: Human papillomavirus genotype distribution in oropharynx and oral cavity cancer in France - the EDiTH VI Study. J Clin Virol 2011;51:100-104.
Huibregtse JM, Scheffner M, Howley PM: A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J 1991;10:4129-4135.
Crook T, Tidy JA, Vousden KH: Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation. Cell 1991;67:547-556.
Munger K, Werness BA, Dyson N, Phelps WC, Harlow E, Howley PM: Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J 1989;8:4099-4105.
Giuliano AR, Lu B, Nielson CM, Flores R, Papenfuss MR, Lee JH, Abrahamsen M, Harris RB: Age-specific prevalence, incidence, and duration of human papillomavirus infections in a cohort of 290 US men. J Infect Dis 2008;198:827-835.
Steben M, Duarte-Franco E: Human papillomavirus infection: epidemiology and pathophysiology. Gynecol oncol 2007;107:S2-S5.
Colson P, de Lamballerie X, Fournous G, Raoult D: Reclassification of giant viruses composing a fourth domain of life in the new order megavirales. Intervirology 2012;55:321-332.
Boyer M, Yutin N, Pagnier I, Barrassi L, Fournous G, Espinosa L, Robert C, Azza S, Sun S, Rossmann MG, Suzan-Monti M, La Scola B, Koonin EV, Raoult D: Giant Marseillevirus highlights the role of amoebae as a melting pot in emergence of chimeric microorganisms. Proc Natl Acad Sci USA 2009;106:21848-21853.
Koonin EV, Yutin N: Origin and evolution of eukaryotic large nucleo-cytoplasmic DNA viruses. Intervirology 2010;53:284-292.
Reed KD, Melski JW, Graham MB, Regnery RL, Sotir MJ, Wegner MV, Kazmierczak JJ, Stratman EJ, Li Y, Fairley JA, Swain GR, Olson VA, Sargent EK, Kehl SC, Frace MA, Kline R, Foldy SL, Davis JP, Damon IK: The detection of monkeypox in humans in the western hemisphere. New Engl J Med 2004;350:342-350.
La Scola B, Marrie TJ, Auffray JP, Raoult D: Mimivirus in pneumonia patients. Emerg Infect Dis 2005;11:449-452.
Vincent A, La Scola B, Forel JM, Pauly V, Raoult D, Papazian L: Clinical significance of a positive serology for Mimivirus in patients presenting a suspicion of ventilator-associated pneumonia. Crit Care Med 2009;37:111-118.
Lagier JC, Armougom F, Million M, Hugon P, Pagnier I, Robert C, Bittar F, Fournous G, Gimenez G, Maraninchi M, Trape JF, Koonin EV, La Scola B, Raoult D: Microbial culturomics: paradigm shift in the human gut microbiome study. Clin Microbiol Infect 2012;18:1185-1193.
Colson P, Fancello L, Gimenez G, Armougom F, Desnues C, Fournous G, Yoosuf N, Million M, La Scola B, Raoult D: Evidence of the megavirome in humans. J Clin Virol 2013;57:191-200.
Popgeorgiev N, Boyer M, Fancello L, Monteil S, Robert C, Rivet R, Nappez C, Azza S, Chiaroni J, Raoult D, Desnues C: Marseillevirus-like virus recovered from blood donated by asymptomatic humans. J Infect Dis 2013, E-pub ahead of print.
Colson P, Pagnier I, Yoosuf N, Fournous G, La Scola B, Raoult D: ‘Marseilleviridae', a new family of giant viruses infecting amoebae. Arch Virol 2013;158:915-920.
Thomas V, Bertelli C, Collyn F, Casson N, Telenti A, Goesmann A, Croxatto A, Greub G: Lausannevirus, a giant amoebal virus encoding histone doublets. Environ Microbiol 2011;13:1454-1466.
Allard A, Albinsson B, Wadell G: Detection of adenoviruses in stools from healthy persons and patients with diarrhea by two-step polymerase chain reaction. J Med Virol 1992;37:149-157.
Kim MS, Park EJ, Roh SW, Bae JW: Diversity and abundance of single-stranded DNA viruses in human feces. Appl Environ Microbiol 2011;77:8062-8070.
Seifi S, Asvadi Kermani I, Dolatkhah R, Asvadi Kermani A, Sakhinia E, Asgarzadeh M, Dastgiri S, Ebrahimi A, Asghari Haggi A, Nadri M, Asvadi Kermani T: Prevalence of oral human papilloma virus in healthy individuals in east Azerbaijan province of Iran. Iran J Public Health 2013;42:79-85.
Korup S, Rietscher J, Calvignac-Spencer S, Trusch F, Hofmann J, Moens U, Sauer I, Voigt S, Schmuck R, Ehlers B: Identification of a novel human polyomavirus in organs of the gastrointestinal tract. PloS One 2013;8:e58021.
Csoma E, Sapy T, Meszaros B, Gergely L: Novel human polyomaviruses in pregnancy: higher prevalence of BKPyV, but no WUPyV, KIPyV and HPyV9. J Clin Virol 2012;55:262-265.
Lin CL, Kyono W, Tongson J, Chua PK, Easa D, Yanagihara R, Nerurkar VR: Fecal excretion of a novel human circovirus, TT virus, in healthy children. Clin Diagn Lab Immunol 2000;7:960-963.
Pride DT, Salzman J, Haynes M, Rohwer F, Davis-Long C, White RA 3rd, Loomer P, Armitage GC, Relman DA: Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J 2012;6:915-926.
Bhattacharya R, Sahoo GC, Nayak MK, Saha DR, Sur D, Naik TN, Bhattacharya SK, Krishnan T: Molecular epidemiology of human picobirnaviruses among children of a slum community in Kolkata, India. Infect Genet Evol 2006;6:453-458.
Payne DC, Vinje J, Szilagyi PG, Edwards KM, Staat MA, Weinberg GA, Hall CB, Chappell J, Bernstein DI, Curns AT, Wikswo M, Shirley SH, Hall AJ, Lopman B, Parashar UD: Norovirus and medically attended gastroenteritis in US children. New Engl J Med 2013;368:1121-1130.
Edwards KM, Zhu Y, Griffin MR, Weinberg GA, Hall CB, Szilagyi PG, Staat MA, Iwane M, Prill MM, Williams JV: Burden of human metapneumovirus infection in young children. New Engl J Med 2013;368:633-643.
Almgren M, Atkinson R, He J, Hilding A, Hagman E, Wolk A, Thorell A, Marcus C, Naslund E, Ostenson CG, Schalling M, Lavebratt C: Adenovirus-36 is associated with obesity in children and adults in Sweden as determined by rapid ELISA. PloS One 2012;7:e41652.
Goel P, Tailor P, Chande AG, Basu A, Mukhopadhyaya R: An infectious HHV-6B isolate from a healthy adult with chromosomally integrated virus and a reporter based relative viral titer assay. Virus Res 2013;173:280-285.
Moens U: Silencing viral microRNA as a novel antiviral therapy? J Biomed Biotechnol 2009;2009:419539.
Chen AC, Keleher A, Kedda MA, Spurdle AB, McMillan NA, Antonsson A: Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donors. J Med Virol 2009;81:1792-1796.
Karimi-Rastehkenari A, Bouzari M: High frequency of SEN virus infection in thalassemic patients and healthy blood donors in Iran. Virol J 2010;7:1.
Bernardin F, Operskalski E, Busch M, Delwart E: Transfusion transmission of highly prevalent commensal human viruses. Transfusion 2010;50:2474-2483.
Afkari R, Pirouzi A, Mohsenzadeh M, Azadi M, Jafari M: Molecular detection of TT virus and SEN virus infections in hemodialysed patients and blood donors in south of Iran. Indian J Pathol Microbiol 2012;55:478-480.
Grossman Z, Mendelson E, Brok-Simoni F, Mileguir F, Leitner Y, Rechavi G, Ramot B: Detection of adeno-associated virus type 2 in human peripheral blood cells. J Gen Virol 1992;73:961-966.
Juhl D, Baylis SA, Blumel J, Gorg S, Hennig H: Seroprevalence and incidence of hepatitis E virus infection in German blood donors. Transfusion 2013, E-pub ahead of print.
Vollmer T, Diekmann J, Johne R, Eberhardt M, Knabbe C, Dreier J: Novel approach for detection of hepatitis E virus infection in German blood donors. J Clin Microbiol 2012;50:2708-2713.
Utba NM: The prevalence of hepatitis E virus in Al-Sadr city - Baghdad. Clin Lab 2013;59:115-120.
Allering L, Jost H, Emmerich P, Gunther S, Lattwein E, Schmidt M, Seifried E, Sambri V, Hourfar K, Schmidt-Chanasit J: Detection of Usutu virus infection in a healthy blood donor from south-west Germany, 2012. Euro Surveill 2012;17:20341.
El-Zayadi AR, Abe K, Selim O, Naito H, Hess G, Ahdy A: Prevalence of GBV-C/hepatitis G virus viraemia among blood donors, health care personnel, chronic non-B non-C hepatitis, chronic hepatitis C and hemodialysis patients in Egypt. J Virol Methods 1999;80:53-58.
Gaibani P, Pierro A, Lunghi G, Farina C, Toschi V, Matinato C, Orlandi A, Zoccoli A, Almini D, Landini MP, Torresani E, Sambri V: Seroprevalence of West Nile virus antibodies in blood donors living in the metropolitan area of Milan, Italy, 2009-2011. New Microbiol 2013;36:81-83.
Gozalan A, Kalaycioglu H, Uyar Y, Sevindi DF, Turkyilmaz B, Cakir V, Cindemir C, Unal B, Yagci-Caglayik D, Korukluoglu G, Ertek M, Heyman P, Lundkvist A: Human puumala and dobrava hantavirus infections in the Black Sea region of Turkey: a cross-sectional study. Vector Borne Zoonotic Dis 2013;13:111-118.
Ergunay K, Aydogan S, Ilhami Ozcebe O, Cilek EE, Hacioglu S, Karakaya J, Ozkul A, Us D: Toscana virus (TOSV) exposure is confirmed in blood donors from central, north and south/southeast Anatolia, Turkey. Zoonoses and public health 2012;59:148-154.
Moens U, Ludvigsen M, Van Ghelue M: Human polyomaviruses in skin diseases. Pathol Res Int 2011;2011:123491.
Silva-Fernandes AT, Travassos CE, Ferreira JM, Abrahao JS, Rocha ES, Viana-Ferreira F, dos Santos JR, Bonjardim CA, Ferreira PC, Kroon EG: Natural human infections with vaccinia virus during bovine vaccinia outbreaks. J Clin Virol 2009;44:308-313.
Osiowy C, Sauder C: Detection of TT virus in human hair and skin. Hepatol Res 2000;16:155-162.
Corcioli F, Zakrzewska K, Fanci R, De Giorgi V, Innocenti M, Rotellini M, Di Lollo S, Azzi A: Human parvovirus PARV4 DNA in tissues from adult individuals: a comparison with human parvovirus B19 (B19V). Virol J 2010;7:272.
Cone RW, Hobson AC, Brown Z, Ashley R, Berry S, Winter C, Corey L: Frequent detection of genital herpes simplex virus DNA by polymerase chain reaction among pregnant women. JAMA 1994;272:792-796.
Rice PS, Mant C, Cason J, Bible JM, Muir P, Kell B, Best JM: High prevalence of human papillomavirus type 16 infection among children. J Med Virol 2000;61:70-75.
Kramer T, Enquist LW: Directional spread of alphaherpesviruses in the nervous system. Viruses 2013;5:678-707.
Chan PK, Ng HK, Hui M, Cheng AF: Prevalence and distribution of human herpesvirus 6 variants A and B in adult human brain. J Med Virol 2001;64:42-46.
Chastel C: Eventual role of asymptomatic cases of dengue for the introduction and spread of dengue viruses in non-endemic regions. Front Physiol 2012;3:70.
De La Torre JC, Gonzalez-Dunia D, Cubitt B, Mallory M, Mueller-Lantzsch N, Grasser FA, Hansen LA, Masliah E: Detection of Borna disease virus antigen and RNA in human autopsy brain samples from neuropsychiatric patients. Virology 1996;223:272-282.

N.P. and S.T. contributed equally to this work.

Open Access License / Drug Dosage / Disclaimer
Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (, applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.