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Transmission of viruses from wildlife to humans continues to cause outbreaks of disease in humans. Examples of recent outbreaks are the Middle East Respiratory Syndrome-coronavirus (MERS-CoV) that may have originated from bats and/or camelids and the influenza A (H7N9) virus that originated from wild birds. A systematic exploration of viruses present in several key host species of wild animals might provide important information to find the original host or carriers of viruses of future outbreaks of viral disease among domestic animals, endangered animal species, and humans. Furthermore, information about the presence of viruses in healthy hosts provides a baseline level for viruses present in these animals in case an outbreak of disease occurs. In previous viral metagenomics studies, high numbers of new viruses have been identified. The results of these studies have highlighted that our knowledge of the viral reservoir is far from complete and many, as yet, unidentified viruses circulate among humans and wild and domestic animals. However, there is an enormous diversity of viral sequences and viral metagenomics efforts should be focused on outbreaks of disease and viral metagenomics on samples collected from a selected number of key species.
Wild carnivores are known carriers of several viral pathogens that can affect domestic animals and humans, including rabies and canine distemper virus. In addition, in previous studies various previously unknown viruses have been detected in European badgers, red foxes and European pine martens in the Netherlands. In the present study, we evaluated the viral diversity of fecal swabs or fecal specimens collected from 10 different small carnivore species of the Mustelidae, Canidae, Viverridae and Felidae families inhabiting northern Spain.
An estimated ~60% of emerging infectious diseases are caused by pathogens which originate from a non-human animal source, referred to as zoonoses (1–3). Moreover, the frequency of outbreaks caused by zoonotic pathogens has been increasing over time in the human population, with viruses being the most successful at crossing the species barrier (2–4). Given the impact of viral zoonoses on global public health, considerable resources have been invested into better understanding patterns in their emergence to improve predictions of where they might arise. One key variable in such predictions is to determine the animal reservoir populations within which these novel viruses can be maintained indefinitely (with or without disease) and which therefore act as sources for transmission to humans (5). In some instances, epidemiological associations may provide clues to identifying a reservoir host species, and the detection of natural infection through seroconversion or the virus itself provides further evidence. Recently, phylogenetic analyses have also been used to investigate viral origins—with a presence of greater diversity and of strains ancestral to those in humans being indicative of a virus circulating within a particular natural host population (6).
Once identified, viral reservoirs have historically been critical levers through which to reduce human cases (5). However, reservoir hosts may also provide us with fundamental insights into host-pathogen interactions and are a rich opportunity to examine the immunological processes that contribute to patterns governing which pathogens cross into humans, cause disease and why (7, 8). This can be particularly informative as in many instances, the zoonotic viruses that are so pathogenic in humans do not cause disease in the reservoirs with which they coexist.
The recent epidemic of Ebola virus in Africa as well as the emergence of a hitherto unknown virus known as Middle East respiratory syndrome coronavirus (MERS-CoV), Bas-Congo virus in central Africa or of severe fever with thrombocytopenia syndrome virus (SFTSV) in China have repeatedly shown the global impact of emerging infectious diseases (EIDs) on economics and public health. These EIDs, more than 60% of which are of zoonotic origin, are globally emerging and re-emerging with increased frequency. Surveillance and monitoring of viral pathogens circulating in humans and wildlife and the identification of EIDs at an early stage is challenging. Many potential emerging viruses of concern might already be infecting humans or wildlife but await their detection by disease surveillance. In remote and underdeveloped regions of the world, often no attention is paid towards possible infectious disease cases until a threshold of serious cases and deaths appears in a cluster and certain epidemic properties are reached. Some viruses might just be overlooked at population levels until they spread or re-emerge and become epidemic in another region or time. An effective strategy in virus surveillance would need to survey simultaneously a wide range of viral types in a large number of human and wildlife individuals in order to detect viruses before spreading. For example, the EcoHealth Alliance within the surveillance program PREDICT seeks to identify new EIDs before they emerge or re-emerge. Therefore, wildlife animals that are likely to carry viruses with zoonotic potential, e.g., bats, rodents, birds and primates, are sampled frequently. However, collecting swabs or blood from sufficient numbers of wildlife individuals and the subsequent identification of viruses is challenging. The solution for overcoming this challenge might be presented by the disease vector itself. Blood feeding arthropods feed on blood from a wide range of hosts including humans, mammals and birds. Therefore, they act as “syringes”, sampling numerous vertebrates and collecting the viral diversity over space, time and species. Xenosurveillance and vector-enabled metagenomics (VEM) are surveillance approaches that can exploit mosquitoes to capture the viral diversity of the animal, human or plant host the mosquito has fed on (Figure 1). Xenosurveillance, a term introduced by Brackney et al., refers to the identification of viral pathogens from total nucleic acids extracted from mosquito blood meals, either by next-generation sequencing (NGS) or conventional PCR assays. Recent developments in NGS and viral metagenomics, which is the shotgun sequencing of viral nucleic acids extracted from purified virus particles, offer great opportunities for the characterization of the complete viral diversity in an organism or a population. VEM, a technique used to sequence purified viral nucleic acids directly from insect vectors, has already been used to detect both animal and plant viruses circulating in vectors. This review summarizes findings from xenosurveillance efforts as well as VEM studies using mosquitoes, since both approaches combine sampling of multiple individuals of blood-feeding arthropods with the high-throughput properties of NGS.
Many infectious diseases in humans are caused by pathogens originating from a wide variety of animals. More than 60% of emerging diseases are estimated to originate from wildlife–. Public awareness of zoonoses has recently increased because of their public health and economic impacts. Birds are recognized as frequent reservoirs for viruses that are of concern to humans; notably influenza A which is capable of infecting other mammals thereby facilitating genome segment reassortments and changes in tropism and transmission efficiency–. Sporadic human infections of the virulent H5N1 resulting from direct contact with infected poultry or wild birds have been reported in 15 countries, mainly in Asia–, and H7N9 has recently emerged as a virus of concern. The prevalence of avian influenza viruses was 12% of oropharyngeal and 20% of cloacal swab specimens collected from urban pigeons in Slovakia. H5N1 was found in a dead feral pigeon in Hong Kong but is generally apathogenic in this host species and the overall risk of H5N1 transmission from pigeons to humans or chickens appears low,. West Nile virus (WNV) and Saint Louis encephalitis (SLE) virus, two arboviruses in the Flavivirus genus transmitted by mosquitoes bites, are disseminated by wild birds–. WNV-specific antibody and viremia was found in 25.7% and 11% of rock pigeons, respectively in the United States. WNV was also isolated in pools of brains, kidneys, heart and spleen of feral pigeons and mapgies. Pigeons developed low levels of WNV viremia; insufficient to infect mosquitoes,. Avian paramyxoviruses, including Newcastle disease virus, are common domestic and wild bird pathogens–. Paramyxovirus type-1 can be found in pigeons worldwide– but the clinical signs vary depending on the immunity of the host and virulence of the specific isolates. While human infection with Newcastle disease virus is rare, at least two outbreaks of conjunctivitis due to Newcastle disease virus have been reported in poultry workers,,. Chicken anemia virus (CAV), until recently the only member of the gyrovirus genus, is highly contagious and causes severe anemia, hemorrhage and depletion of lymphoid tissue in chickens–. Related gyroviruses were recently characterized in human feces, blood and on healthy human skin– indicating possible human tropism. Gyrovirus DNA was also detected in three blood samples of solid organ transplant patients and in one HIV-infected person as well as in 0.85% of healthy French blood donations.
Pigeons are therefore natural reservoirs for pathogens that have caused emerging and re-emerging diseases in humans. In order to better understand the viruses shed by pigeons to which humans are frequently exposed, we genetically characterized the viral community in droppings from wild pigeons in Hong Kong and Hungary following an unbiased amplification method and deep sequencing.
Parvoviruses are non-enveloped single-stranded DNA viruses which infect a wide range of mammalian species, including several members of the order Carnivora. The Carnivore protoparvovirus 1, belonging to genus Protoparvovirus, family Parvoviridae, subfamily Parvovirinae, includes several closely related autonomous viruses causing a range of serious conditions, especially in young animals: feline panleukopenia virus (FPV, the prototype virus of the former carnivore parvovirus), canine parvovirus (CPV), mink enteritis virus (MEV), and raccoon parvovirus (RaPV).
Feline panleukopenia virus has been known to be a cause of disease in cats since the beginning of the twentieth century, although there are other similar parvovirus species affecting cats, such as MEV and CPV. Natural infections in cats with CPV have been reported but FPV remains the most prevalent parvovirus causing disease in cats [2–4]. Since cats are susceptible to FPV and CPV 2a, 2b, 2c variants, superinfection and co-infection with multiple parvovirus strains associated with high viral genetic heterogeneity can occur with relatively high frequency in feline hosts [3, 5–7].
Parvoviruses commonly cause acute infection with high levels of viral shedding which generally ceases within 1–2 weeks post-infection, after the development of high titres of virus-neutralising antibody [8, 9]. Nevertheless, parvoviruses can be detected in faeces forup to 6 weeks after recovery, depending on the sensitivity of the diagnostic method used. Cats experimentally infected with FPV shed the virus in both urine and faeces up to day 41–42 post-infection with parvovirus persisting in the lungs and kidneys for more than 50 weeks in cats which have recovered. The detection of FPV and CPV variants in apparently healthy cats suggests that parvovirus infection may be common in some populations of clinically normal cats, and that asymptomatic cats may be able to shed parvovirus for prolonged periods of time [12–14]. Furthermore, the ability of FPV and CPV to persist in the peripheral blood mononuclear cells (PBMC) of cats irrespective of the presence of neutralising antibodies [13–17] and the presence of parvoviral DNA in the bone marrow of healthy cats, suggests that parvovirus may persist long term in the tissues of cats post-infection without causing clinical signs.
The aim of this study was to screen a population of 54 cats from Sardinia (Italy) for the presence of both FPV and CPV DNA within buffy coat samples. The DNA viral load, genetic diversity, phylogeny and antibody titres against parvoviruses were investigated in the cats testing positive to DNA parvoviruses.
Astroviruses (AstVs) are non-enveloped, positive-sense, single-stranded RNA viruses belonging to the Astroviridae family. Currently, two genera: namely Mamastrovirus and Avastrovirus are distinguished within this family. The genus Mamastrovirus includes astrovirus species isolated from humans and a number of mammals. Isolates originated from avian species, such as turkey, chickens, ducks, and other birds are classified into the genus Avastrovirus1, 2. AstVs have been detected in humans and a variety of animal species, including non-human primates, other mammals and avian species3–5. Their genomes are 6.8–7.9 kb in length, consisting of a 5′-untranslated region (UTR), three open reading frames (ORFs), a 3′-UTR and a poly (A) tail6. The high degree of genetic diversity among AstVs and their recombination potential signify their capacity to cause a broad spectrum of diseases in multiple host species3, 7, 8. Human classical AstVs are a frequent cause of acute gastroenteritis in young children and the elderly, occasionally with encephalitis8.
In poultry, AstV infections have been found to be associated with multiple diseases, such as poult enteritis mortality syndrome, runting-stunting syndrome of broilers, white chick syndrome, kidney and visceral gout in broilers and fatal hepatitis of ducklings, leading to substantial economic losses9–16. Increasing evidence indicates that there is a high degree of cross species transmission of AstVs between domestic birds, and even the potential to infect humans17. By comparison, fewer AstV infection cases have been described in domestic goose flocks. Bidin et al.18 reported the detection of avian nephritis virus infection in Croatian goose flocks and provided evidence that this AstV was associated with stunting and pre-hatching mortality of goose embryos. Studies to detect AstV genomes from the clinical samples of geese suggested that these viruses might distribute widely among goose flocks, as seen in other poultry flocks19, 20. In February 2017, an outbreak of disease was reported in a goose farm in Weifang, Shandong Province, China. Affected flocks (containing 2000–3000 goslings) experienced continuous mortality rates ranging from 20 to 30% during the first 2 weeks of the outbreak despite antibiotic and supportive treatment. We conducted a systematic investigation to identify the causative agent of this disease and report here the isolation and characterization of a genetically distinct avian AstV. The pathogenicity of this virus was evaluated by experimental infection of goslings.
Canine diarrhea is one of the most common illnesses treated by veterinarians with many possible causes of canine diarrhea, including bacteria, parasites, and viruses. One of the most important dog enteric viruses is canine parvovirus 2 (CPV-2) in the Carnivore protoparvovirus species 1. Parvoviruses are small, icosahedral, nonenveloped, single-stranded DNA viruses that are pathogenic to a variety of mammals. The vertebrate-infecting parvoviruses are classified in the subfamily Parvovirinae in the Parvoviridae family (which also includes the insect infecting subfamily Densovirinae). The Parvovirinae subfamily is currently subdivided into eight officially recognized genera (Dependoparvovirus, Copiparvovirus, Bocaparvovirus, Amdoparvovirus, Aveparvovirus, Protoparvovirus, Tetraparvovirus, and Erythroparvovirus). The recently proposed genus Chapparvovirus is currently comprised of a rat parvovirus 2 (KX272741), Eidolon helvum fruit bat parvovirus 1 (MG693107.1), and E. helvum bat parvovirus 2 (JX885610), Desmodus rotundus bat parvovirus (NC032097.1), simian parvo-like virus 3 (KT961660.1), Turkey parvovirus TP1-2012/Hun (KF925531), porcine parvovirus 7 (KU563733), murine chapparvovirus (MF175078), Tasmanian devil-associated chapparvovirus strains 1–6 (MK513528-MK53533), red-crowned crane-associated parvovirus (KY312548, KY312549, KY312550, KY312551), and chicken chapparvovirus 1 and 2 (MG846441 and MG846642). A close relative of murine chapparvovirus, initially reported in the feces of a wild Mus musculus from New York City, called murine kidney parvovirus (MH670588) was recently shown to cause nephropathy in immunocompromised laboratory mice. A recent survey of eukaryotic genomes for chapparvovirus sequences has also shown the presence of a likely exogeneous chapparvovirus genome in a fish (Gulf pipefish or Syngnathus scovelli) and of mostly defective germline sequences in another fish (Tiger tail seahorse or Hippocampus comes) as well as in multiple invertebrates, indicating an ancient origin for chapparvoviruses. A phylogenetic analysis of NS1 also indicated chapparvoviruses fall outside the traditional vertebrate-infecting Parvovirinae subfamily clade and closer to that of a subset of members of the subfamily Densovirinae.
Here an unexplained diarrhea outbreak among dogs was analyzed using viral metagenomics after diagnostic tests were negative for common canine enteric pathogens. The genome of a novel chapparvovirus was characterized and used to perform an epidemiological study to measure its prevalence and possible clinical significance.
Over the past two decades, there has been mounting interest in the increasing number of viruses causing unexpected illness and epidemics among humans, wildlife and livestock. All too often outbreaks have seriously stretched both local and national resources at a time when health-care spending in the economically developed world has been constrained. Importantly, capacity to identify and control emerging diseases remains limited in poorer regions where many of these diseases have their origin.
Emerging disease is a term used with increasing frequency to describe the appearance of an as yet unrecognized infection, or a previously recognized infection that has expanded into a new ecological niche or geographical zone and often accompanied by a significant change in pathogenicity.1 The key message is that these are representative of constantly evolving infections responding to rapid changes in the relationship between pathogen and host.
Among 1400 pathogens of humans over 50% of these have their origins in animal species, that is, “are diseases or infections naturally transmitted between vertebrates and humans” (World Health Organization). According to Woolhouse and colleague2 emerging or re-emerging pathogens are far more likely to be zoonotic. Viruses are over-represented in this group. Moreover, viruses with RNA genomes account for a third of all emerging and re-emerging infections. Emerging pathogens are typically those with a broad host range, often spanning several mammalian orders. Almost certainly many of these infections have been the result of the development of agricultural practices and urbanization (Figure 1).
Recent interest in emerging infections has focused on three key areas. First, how the interplay of climate, environment and human societal pressures can trigger unexpected outbreaks of emerging disease. Second, the understanding of how viruses can transmit between a reservoir and new host species, Third, identifying those aspects of the disease process that offer opportunities for therapy and prevention. To these must be added a broader understanding of how viruses evolve over time, clues to which are now being uncovered through looking closely at genetic elements of the host genome responsible for resisting virus invasion. Meeting these objectives will provide a more rigorous basis for predicting virus emergence.
Infectious viral diseases, both emerging and re-emerging, pose a continuous health threat and disease burden to humans. Many important human pathogens are zoonotic or originated as zoonoses before adapting to humans–. This is exemplified by recently emerged diseases in which mortality ranged from a few hundred people due to infection with H5N1 avian influenza A virus to millions of HIV-infected people from acquired immunodeficiency syndrome–. Severe acute respiratory syndrome (SARS) coronavirus and the pandemic influenza A/H1N1(2009) virus in humans were linked to transmission from animal to human hosts as well and have highlighted this problem–. An ongoing systematic global effort to monitor for emerging and re-emerging pathogens in animals, especially those in key reservoir species that have previously shown to represent an imminent health threat to humans, is crucial in countering the potential public health threat caused by these viruses.
Relatively few studies have been conducted on diseases of non-domestic carnivores, especially regarding diseases of small carnivores (e.g. mustelids). Ferrets (Mustela putorius furo) can carry bacteria and parasites such as Campylobacter, Giardia, and Cryptosporidium in their intestinal tract and potentially spread them to people,. In addition, they can transmit influenza A virus to humans and possibly on rare occasions rabies virus as well–. Because of their susceptibility to several human respiratory viruses, including human and avian influenza viruses, SARS coronavirus, nipah virus, and morbilliviruses–, ferrets have been used as small animal model for these viruses. To further characterize this important animal model and to obtain epidemiological baseline information about pathogens in ferrets, the fecal viral flora of ferrets was studied using a metagenomics approach. Both known and new viruses were identified.
Poxviruses are double-stranded DNA viruses with large genomes (up to 300 kb) belonging to the family Poxviridae. The family is divided into the invertebrate-infecting entomopoxvirinae and chordate-infecting chordopoxvirinae. The latter subfamily is further divided into ten genera and contains many important infectious agents of both animals and humans. The now-eradicated Variola virus (VARV, the causative agent of smallpox) illustrates the potential consequences of poxvirus infections having arguably caused more deaths in human history than any other infectious agent. Aside from humans, chordopoxviruses are also found in a multitude of terrestrial, aquatic and arboreal animal species from diverse taxa e.g., crocodiles, sea lions, birds, camels, etc. and many poxviruses are capable of infecting multiple host species and cause cross-species (including zoonotic) infections. For example, monkeypox virus has been recognized as a zoonotic agent since the 1970s and is classed a bioterrorism agent. Further to human disease burdens, cross species infections of poxviruses between non-human species can also have devastating consequences e.g., the near-extinction of red squirrels in the UK after the introduction of squirrelpox with grey squirrels from the USA. Owing to the significance of these zoonotic and cross-species poxvirus infections, poxvirus host range is a key area of research.
Poxviruses exhibit a heterogeneous host range with some poxviruses having a very broad host range (e.g., cowpox infects rodents, dogs, cats, horses, cows, primates including humans), and others being very specific (e.g., VARV is a human only pathogen). Although some poxvirus genera are known to exhibit broad host tropisms (e.g., orthopoxviruses) and are consequently thought to manifest greater zoonotic risks, phylogenetic relatedness among viruses is not indicative of poxvirus host range. In fact, determinants of poxvirus host range are poorly understood and viral tropism is not typically restricted at the level of cellular entry. Due to highly conserved virion proteins, most poxviruses can enter a wide variety of host cell types, with restriction of infection occurring downstream of entry (either through a lack of host factors or through the innate immune system). Consequently, changes in poxvirus host range are typically determined by changes in virus genome complement (e.g., gene duplication/gain/loss) that allow for subversion of host restriction rather than point mutations, as is the case for some viruses e.g. parvovirus and influenza. Genes that are known to cause shifts in poxvirus host range generally have functions relating to the interplay of the host innate immune mechanisms with the virus. These genes are termed poxvirus host range genes and although approximately 15 have already been identified, more work is needed to fully understand their restriction mechanisms and to identify novel determinants of poxvirus host range.
Bats are an ancient, highly diverse order of mammals that are known to be reservoirs for a large number of viruses. “Bats” is the collective term for some approximately 1200 species of mammals thought to have diverged some 50 million years ago (mya; comparatively humans and great apes are thought to have diverged ~5 mya). Second only in diversity to rodents, bats are subdivided into two suborders, commonly called megabats and microbats, on the basis of behavioral and physiological traits as well as molecular evidence. There has been a recent increase in interest regarding the relationship of bats with viruses (Figure 1) as some species of bats are reservoir hosts for lethal viral zoonoses such as SARS coronaviruses, paramyxoviruses (e.g., Nipah and Hendra viruses), and filoviruses (e.g., Ebola and Marburg virus) and numerous lyssaviruses. Outbreaks of disease attributable to bat-related zoonoses have high economic and human costs and their discovery has resulted in concerted research effort to isolate and characterize viruses from bat populations. Consequently, large numbers of previously unknown viruses have since been identified in bat populations for which the zoonotic potential is unknown, including novel influenza types and hepadnaviruses. As a result, there has been well-grounded speculation that owing perhaps to physiological, ecological, evolutionary, and/or immunological reasons, bats may have a “special” relationship with viruses and be particularly good viral reservoirs with exaggerated viral richness. Indeed, a recent intensive study found that a single bat species likely carries ≥58 different viral species from only nine viral families. As well as the obvious first step of considering the zoonotic potential of newly identified bat viruses, further exploring the impacts of these findings and the opportunities they present for multiple research fields is necessary to capitalize on these discoveries.
Poxvirus infections have recently been identified in bats, comprising part of the increase in viral families newly identified in this taxonomic order. Here, we review the current evidence of poxvirus infections in bats, present the phylogenetic context of the viruses within the Poxviridae, and consider their zoonotic potential. Finally, we speculate on the possible consequences and potential research avenues opened following this marrying of a pathogen of great historical and contemporary importance with an ancient host that has an apparently peculiar relationship with viruses; a fascinating and likely fruitful meeting whose study will be facilitated by recent technological advances and a heightened interest in bat virology.
Canine enteritis can be caused by a number of viral, bacterial or parasitic agents. The most common viral entero-pathogens are canine parvovirus (CPV) and coronavirus (CCoV),, although other agents, such as canine adenovirus (CAdV) type 1, canine distemper virus (CDV), rotaviruses, reoviruses, and caliciviruses, have been associated with enteric disease in dogs. In recent years, novel viruses have been discovered from dogs with enteritis, namely noroviruses, sapoviruses, astroviruses, and kobuviruses,.
More recently, a dog circovirus (DogCV) was detected in dogs with vasculitis and/or hemorrhagic diarrhoea in the US (13). Circoviruses (family Circoviridae, genus Circovirus) are non-enveloped, spherical viruses with a small monomeric single-strand circular DNA genome of about 2 kb in length. According to the most recent release of the Universal Virus Database of the International Committee on Taxonomy of Viruses, the genus Circovirus consists of eleven recognized species, including Porcine circovirus 1 (PCV-1), Porcine circovirus 2 (PCV-2), Canary circovirus (CaCV), Beak and feather disease virus (BFDV), and other viruses of domestic and wild birds (http://ictvdb.bio-mirror.cn/Ictv/fs_circo.htm). Porcine and avian circovirus infections are characterized by clinical courses that may vary from asymptomatic infections to lethal disease.
Two independent studies have shown that, similar to other animal circoviruses, DogCV possesses an ambisense genomic organization with 2 major inversely arranged ORFs encoding for the replicase and capsid proteins, respectively,. The canine virus, firstly detected in serum samples, was later recognized as causative agent of necrotizing vasculitis and granulomatous lymphadenitis.
The aim of this paper is to report the detection and molecular characterisation of DogCV in dogs with acute gastroenteritis in Italy. The full-length genome of the Italian prototype strain was determined and analyzed in comparison with American strains and other circoviruses.
Following on from the discovery of tobacco mosaic virus in 1892 and foot-and-mouth disease virus in 1898, the first ‘filterable agent’ to be discovered in humans was yellow fever virus in 1901. New species of human virus are still being identified, at a rate of three or four per year (see below), and viruses make up over two-thirds of all new human pathogens, a highly significant over-representation given that most human pathogen species are bacteria, fungi or helminths. These new viruses differ wildly in their importance, ranging from the rare and mild illness due to Menangle virus to the devastating public health impact of HIV-1.
In this paper, we take an ecological approach to studying the diversity of human viruses (defined as viruses for which there is evidence of natural infection of humans). First, we describe and analyse temporal, geographical and taxonomic patterns in the discovery of human viruses (§2). We then consider the processes by which new human viruses emerge (§3). There are a number of definitions of ‘emergence’; here, we are interested in all stages of the process by which a virus shifts from not infecting humans at all to becoming a major human pathogen. As experiences with HIV-1 and new variants of influenza A (and also with novel animal pathogens such as canine parvovirus) show, this shift can occur rapidly, over time scales of decades, years or even months.
Of course, not all newly identified human virus species are ‘new’ in the sense that they have only recently started to infect humans; many of them have been present in humans for a considerable time but have only recently been recognized (see for a more detailed discussion). Moreover, we recognize that ‘species’ itself is an imprecise designation, especially for viruses such as influenza A where different serotypes can have very different epidemiologies and health impacts. Indeed, the demarcation between genus, species complex, species and serotype (or other designations of sub-specific variation) can be somewhat arbitrary. Nonetheless, a study of currently recognized ‘species’ is a natural starting point for attempts to characterize and interpret patterns of virus diversity.
Using random amplification in combination with next-generation sequencing, more than 320,000 trimmed sequence reads were obtained of fecal samples collected from the carnivores of the present study (Figure 1). Reads were classified into eukaryotic viruses, phages, bacteria and eukaryotes. Many of the identified sequences were of bacterial or eukaryotic origin. A substantial proportion of the reads did not have any significant hits for nucleotide or amino acid sequences in GenBank. In addition, several reads were detected that had the closest similarity to viruses. In the majority of the samples, sequences of the order Caudovirales were detected and in 26 out of 42 samples, sequences were detected that had the closest similarity to viruses known to infect eukaryotes (Figure 2A, Table 1). Viruses belonging to the families of Anelloviridae, Astroviridae, Bunyaviridae, Caliciviridae, Circoviridiae, Parvoviridae subfamily Parvovirinae, Picobirnaviridae, Picornaviridae, Rhabdoviridae, and Retroviridae were detected (Figure 2B). Furthermore, sequences were detected that had the closest similarity to the recently proposed family of Breviviridae and the recently described hybrid DNA virus NIH-CQV/PHV which was identified as a contaminant of silica column-based nucleic acid extraction kits. No sequences were detected that were identical to currently known zoonotic viruses. A proportion of the detected viral sequences had the closest similarity to viruses previously detected in birds and rodents. For example, in an European mink (sample 26), sequences were detected with >95% homology on the nucleotide level with Turkey parvovirus and in a stone marten (sample 41), sequences were detected with 94-96% homology on the nucleotide level with Encephalomyocarditis virus type 2 isolate RD 1338 (D28/05) detected in a wood mouse (Apodemus sylvaticus). These viruses most likely originate from the diet of the animals. In addition, sequences with >95% identity on the nucleotide level to viruses that are known to infect mink were detected in European and American mink, including Mink calicivirus strain MCV-DL/2007/CN (samples 1 and 8) and Aleutian mink disease virus (sample 30). Antibodies to Aleutian mink disease parvovirus have been detected in a cohort of free-ranging European mink in southwestern France and northern Spain previously, but not in another cohort of free-ranging European mink in Navarra, Spain. Additional sampling and confirmation by specific PCR is necessary to indeed confirm that the Aleutian mink disease parvovirus is circulating among these animals. Besides these sequences that had high homology with known viruses, also sequences were detected that had the closest similarity to viruses, but with only low homology. A number of sequences of potentially novel viruses or virus variants, including a theilovirus, phleboviruses, an amdovirus, a kobuvirus and picobirnaviruses, were further characterized in the present manuscript, while sequences of the other viruses are preliminary and need further characterization.
Influenza viruses comprise 4 types: A, B, C, and D. Influenza A viruses are further classified into subtypes on the basis of the characteristics of the 2 main surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), and numbered accordingly. While only 2 influenza A virus subtypes (H3N2 and H1N1pdm09) are circulating among humans, the natural reservoir for nearly all influenza A viruses is wild waterfowl. Of the 18 HA and 11 NA influenza A virus subtypes, all but H17N10 and H18N11 viruses have been identified in birds. Some influenza A viruses circulate among pigs, and others have been identified in a wide number of animal species.
Only influenza A viruses cause seasonal influenza epidemics and rare pandemics among people. Influenza B viruses can cause seasonal epidemics, influenza C viruses typically cause mild respiratory illness and do not cause epidemics, and influenza D viruses primarily affect cattle and are not known to cause illness in people.9
Novel influenza A viruses refer to viruses of animal origin that have infected humans and that are antigenically and genetically distinct from seasonal influenza A viruses circulating among people. We closely monitor novel influenza A viruses, because influenza A viruses continue to evolve and because zoonotic transmission could herald an increasing pandemic influenza health threat. If a novel influenza A virus acquires the ability for sustained human-to-human transmission, a pandemic can result. Accordingly, early detection of pandemic-potential viruses may aid in the control and possible prevention of the next pandemic. Although a swine-origin influenza A virus caused the 2009 H1N1 pandemic,10,11 and sporadic transmission of swine-origin influenza A viruses to humans (termed “variant viruses”) continue to be detected in the United States and in other countries with appropriate laboratory capacity, the public health threat posed by avian influenza A viruses appears to be higher because of their diversity and wide circulation among birds worldwide; the birds' migratory flyways may also be conducive to spread of influenza A viruses. Furthermore, some previous pandemic influenza A viruses have been partly of avian origin.11
Evidence of PARV4 infection is most frequently detected by an ELISA for specific IgG antibody to VP-2. This response appears to be sustained over time, as with other parvovirus infections; weak or transient VP-2 IgM positivity has also been reported in acute infection.
PARV4 DNA may be isolated from plasma in acute infection, generally with low viral loads (e.g. ≤3×104 copies/ml),, although acute viraemia of up to 1010 copies/ml has been reported. Asymptomatic viraemia was reported in 8% of children in a Ghanaian cohort. Different studies have reported the duration of viraemia lasting from 30 days up to a mean of 7 months. However, recrudescence or reinfection could also explain these relatively prolonged durations of viraemia. Despite these reports of isolation of PARV4 DNA from serum,,, this is generally uncommon, suggesting that immune containment is good even in immunocompromised hosts.
Human bocavirus (HBoV) was discovered in 2005 by Allander et al. in respiratory samples from children with suspected acute respiratory tract infection (ARTI) using a novel technique. This molecular virus screening is based on a random PCR-cloning-sequencing approach and was employed on two chronologically distinct pools of nasopharyngal aspirates (NPAs). It revealed a parvovirus-like sequence, with close relation to the members of the bocavirus genus.
A retrospective study revealed 17 (3.1 %) out of 540 NPAs positive for HBoV, with 14 specimens tested negative for other viruses, giving the suggestion that HBoV is a causative agent of respiratory tract infections.
Viruses of the genus Orthohepadnavirus, family Hepadnaviridae, are partially double-stranded DNA viruses that infect a variety of mammals. Chronic infections in humans of the prototype species, hepatitis B virus (HBV), increase the risk of liver diseases including cirrhosis and hepatocellular carcinoma1.
Hepadnaviruses have been identified in several animal species including primates, bats, rodents, birds and fish2. Recently a novel member of the family Hepadnaviridae, similar to HBV, has been identified through transcriptomics studies in a domestic cat with large cell lymphoma3. Preliminary epidemiological data collected by Australian researchers suggest that the hepadnavirus of domestic cat (DCH) is common in cats infected with feline immunodeficiency virus (FIV)3. In order to gather additional information on DCH, we analyzed sera collected from household cats with different age (0–15 years) and clinical histories, obtained from veterinary diagnostic laboratories.
The parvoviruses are a group of small, non-enveloped animal viruses with a single-stranded DNA genome between 4 and 6 kb in size. At least 2 open reading frames (ORF) are present in the parvovirus genome, with ORF1 encoding the non-structural proteins and ORF2 encoding the viral capsid proteins. Some parvovirus genomes may contain an additional ORF encoding for other proteins, such as the non-structural protein NP1 found in human bocavirus and bovine parvovirus. Under the current International Committee on Taxonomy of Viruses (ICTV) classification system, the Parvoviridae are divided into two subfamilies based on their host range: the Parvovirinae which infect vertebrates, and the Densovirinae which mainly infect insects and other arthropods. The Parvovirinae are further subdivided into 5 genera: the amdoviruses, bocaviruses, dependoviruses, erythroviruses, and the parvoviruses. Novel parvoviruses discovered in recent years, such as the human partetravirus (previously known as human parvovirus 4 or PARV4), are not included in the current classification system, and will be addressed by the ICTV in an upcoming update.
Some human parvoviruses are well-known pathogens associated with a range of diseases in infected patients. Parvovirus B19 (also known as erythrovirus B19) can cause syndromes ranging from erythema infectiosum in children to late intrauterine death in pregnant women. The human bocavirus, a parvovirus discovered only in 2005, was associated with respiratory disease and could be detected in stool of children,,,,,, although clear assessment of its pathogenicity is confounded by the frequent co-detection of other respiratory viruses, and its presence in the stool of healthy children. On the other hand, the human partetravirus was initially discovered in patients suffering from acute viral syndrome, but its association with clinical disease has yet to be confirmed despite positive PCR detection in blood products, HIV-infected patients, intravenous drug users, transplant patients and blood donors in different localities,,,,,,,.
Since the discovery of the human partetravirus, related animal viruses have been found in various mammalian species. We first reported the discovery of porcine and bovine partetraviruses (also known as hokoviruses previously), which are novel related animal parvoviruses found in Hong Kong. Closely related porcine partetraviruses have since been found in German wild boar populations, while human partetravirus-like viral DNA was detected in the plasma samples of a chimpanzee and baboon in Cameroon. As the genetic distances between human partetravirus and other known parvoviruses at the time of its discovery were relatively large, it was unclear if the human partetravirus had diverged from a human parvovirus ancestor early in the history of parvovirus evolution or if it had diverged from an undiscovered animal parvovirus. Parvovirus evolution is characterized by the development of host-specificity and congruent viral and host phylogenies, which has led to the hypothesis of long-term co-evolution of parvoviruses and their hosts. In addition, evolutionary rates can vary significantly among different parvovirus species,, which complicates evolutionary analysis between distant parvoviruses. Hence, the identification of related partetraviruses in animals has contributed to our knowledge of the evolutionary history of the human partetravirus.
As part of our ongoing program in the discovery of viruses associated with emerging infections, we continued our surveillance for novel partetraviruses in animals closely related to humans. In the present study, bovine and ovine samples were selected for targeted screening, as both domestic cattle and sheep are important food animals in Southern China. PCR screening of the animal samples identified a novel ovine partetraviruses as well as a new genotype of bovine partetravirus, and their nearly full-length genome sequences were obtained. Genomic and phylogenetic analyses of the new viruses confirmed them to be closely related to the previously identified partetraviruses.
The virome is the community of viruses found in a particular ecosystem. Viromes characterized from animals and human are comprised of both prokaryotic and eukaryotic viruses. Commensal bacteriophages, which make up the major fraction of the fecal virome, can modulate the microbial community in the host body and influence host immunity. Although typically a smaller fraction of the enteric virome, mammalian viruses may cause diseases such as diarrhea resulting in malnutrition and dehydration. Deep sequencing of wild animal fecal viromes also unveiled many eukaryotic viruses whose pathogenicity, if any, remain mostly unknown. In the past, emergences of human infectious diseases have been initiated by zoonotic viruses originating from bats, rodents, and non-human primates. Ebola virus likely from bats, human immunodeficiency virus (HIV) from chimpanzees, and the Middle East respiratory syndrome coronavirus (MERS-CoV) from camels, have caused very large economic and public health disruptions. Therefore, it is important to identify the viruses within animals with the potential to spill over into human and result in pathogenic infections. Such zoonoses may take different routes including fecal-oral transmission. Outbreaks of zoonotic enteric viruses belonging to the families of Picornaviridae, Adenoviridae, Caliciviridae, and Reoviridae cause important enteric diseases in humans. Moreover, alteration of enteric virome in humans also affect bacterial microbiome stability and influence diseases such as inflammatory bowel disease and ulcerative colitis. Studies of intestinal and fecal bacterial communities have received much attention relative to that of the gut virome.
Cynomolgus macaque, a non-human primate species widely distributing across Southeast Asian countries have long been used for biological research including on influenza virus, Ebola virus, and simian/human immunodeficiency virus (SIV/HIV). The National Primate Research Center of Thailand–Chulalongkorn University (NPRCT-CU), maintains a colony of cynomolgus macaques captured from disturbed natural habitats. Although well-established biosecurity protocols are used to screen infectious viruses such as herpes B virus, simian retrovirus (SRV), simian immunodeficiency virus (SIV), simian-T-lymphotropic viruses (STLV) and foamy virus that might cause a sporadic outbreaks, the transmission of other viruses from wild-originating macaques remains possible. In addition, captivity may also influence gut microbiome and virome. A recent study illustrated that replacing the gut microbiome of inbred laboratory mice with that of wild mice restored their immune responses to better mimic those of wild animals. Here, we characterized and compared the fecal virome of wild and captive macaques and identified novel macaque viruses.
There is currently no definitive clinical syndrome associated with PARV4 infection, and the potential pathogenicity of related hokoviruses in animals is also unknown. In the majority of instances, PARV4 viraemia appears to be self-limiting and asymptomatic, and there is no consistent association with increased severity of co-existing blood-borne viruses.
However, in a minority of reports, a range of possible disease outcomes are described in individuals with evidence of past or current PARV4 infection, including respiratory or gastrointestinal symptoms, hepatitis, rash, and encephalitis (Table 1). Notably, most of these studies describe small numbers of patients, and none is definitively able to attribute clinical manifestations to the presence of PARV4. Establishing cause and effect is further confounded by the close relationship between PARV4 and other blood-borne viruses; for example, although a statistical correlation has been described between PARV4 positivity and early features of AIDS, this association is potentially confounded by the close relationship between PARV4 and both HCV status and individuals with a history of IDU.
Arthropods can act as biological vectors that transmit infectious agents and thereby cause diseases in humans and animals. After mosquitoes, ticks are the most common arthropod vector for viruses, bacteria, and other parasites causing different vector-borne diseases. Ticks from different parts of the world have been shown to carry viruses belonging to, for example, the Bunyaviridae, Flaviviridae, Asfaviridae and Orthomyxoviridae families. Additionally, ticks carry many non-pathogenic microbes, and some of these microbes have formed symbiotic relationships with their hosts and transmit by vertical transmission [2–5].
The genus Rhipicephalus, belonging to the Ixodidae family (family of hard ticks), is widely distributed worldwide and is considered a potential vector of several emerging pathogens. Different studies have shown that viral pathogens, such as Thogoto viruses, Wad Medani virus, Nairobi sheep disease virus, Crimean-Congo hemorrhagic fever virus, African swine fever virus and Tick-borne encephalitis virus [1,6–8], can be found in Rhipicephalus ticks. Borrelia, Anaplasma, Rickettsia, Ehrlichia, and Babesia are a few examples of the pathogenic bacteria that have been identified in these types of ticks.
With the advent of metagenomic approaches, the limitations of culture-based methods have been overcome and have enabled the characterization of the entire microbiota associated with the host. Numerous studies have used metagenomics to explore viral communities in different arthropod species and have in these identified viruses associated with a broad range of animals, plants and insects. Many of the identified viruses have been novel, for example, highly divergent viruses belonging to nairoviruses and phleboviruses were reported in Amblyomma and Ixodes ticks from the USA [11–13] and in Rhipicephalus ticks.
Previous reports indicate that many tick-borne disease-causing agents exist in Mozambique, such as Nairobi sheep disease virus, Theleiria and Anaplasma. Since ticks are known vectors for potentially pathogenic and non-pathogenic viruses and the virome of ticks is understudied in this region, the current study used viral metagenomics to identify viruses associated with Rhipicephalus ticks collected in the Zambezi Valley of Mozambique.
Canine parvovirus type 2 (CPV-2) is one of the most dangerous enteropathogens, causing fatal disease in dogs and puppies worldwide. CPV-2 is a nonenveloped, small DNA virus with a diameter of approximately 25 nm and a single-stranded DNA genome of approximately 5 kb. CPV-2 belongs to the genus Parvovirus in the family Parvoviridae, which includes feline panleukopenia virus (FPV), mink enteritis virus, raccoon parvovirus, and porcine parvovirus. Clinical manifestations of CPV-2 infection are characterized by intestinal hemorrhage with severe bloody diarrhea; other clinical signs include anorexia, depression and vomiting [1, 3, 4].
CPV-2 is a rapidly evolving virus, leading to the mutation of novel variants since its first recognition in the late 1970s. For example, CPV-2a was approximately discovered in 1980 in the USA, and CPV-2b and 2c were identified in 1984 and 2000 in the USA and Italy, respectively, based on residue 426 (Asn in 2a, Asp in 2b, and Glu in 2c) in the VP2 protein of the parvovirus [4, 6]. When a novel CPV-2 variant appears, it very rapidly replaces old variants [7, 8]. In recent decades, CPV-2c has been found to be widespread in European countries [1, 9], the USA, South America [11–13] and Africa [14, 15]. The first reported occurrence of the CPV-2c variant in Vietnam was in 2004; however, since then, this strain has not been prevalent in Asia. Surprisingly, novel Asian CPV-2c isolates were identified in China [18–21], Taiwan [17, 22], Laos and Thailand in the past few years.
In Vietnam, CPV-2 infection was first observed as sporadic cases in 1994 (unpublished data). Subsequently, after its first emergence, there were widespread outbreaks of canine hemorrhagic enteritis with high morbidity and mortality occurring across the whole country. Along with the increasing number of pet dogs in Vietnam, CPV-2 infection has emerged as a veterinary public health concern that greatly affects puppies because of its high mortality and morbidity. However, current information related to the antigenic types of CPV prevailing in Vietnam is poorly understood. Thus, in the present study, we investigated the genotype prevalence and distribution of CPV-2 from naturally infected dogs in three regions of Vietnam using a SimpleProbe® real-time polymerase chain reaction (PCR) assay.
HBoV is a putative member of the family Parvoviridae, subfamily Parvovirinae, genus Bocavirus. Before identification of HBoV, parvovirus B19 of the genus Erythrovirus was the only known human pathogen in the family of parvoviruses. Parvovirus B19 is widespread and manifestations of infection vary with the immunologic and hematologic status of the host. In immunocompetent children, parvovirus B19 is the cause for erythema infectiosum. In adults it has been associated with spontaneous abortion, non-immune hydrops fetalis, acute symmetric polyarthropathy, as well as several auto-immune diseases.
Based on its genomic structure and amino acid sequence similarity shared with the namesake members of the genus, bovine parvovirus (BPV) and canine minute virus (MVC), HBoV was classified as a bocavirus and therefore provisionally named human bocavirus.
Other subfamily Parvovirinae members known to infect humans are the apathogenic adeno-associated viruses of the genus Dependovirus and parvovirus 4. Parvovirus 4 has not yet been assigned to a genus, but it was proposed to allocate it to the genus Hokovirus as it shares more similarities to the novel porcine and bovine hokoviruses than with other parvoviruses. Recently a second human bocavirus has been identified, HBoV2, with 75.6 % nucleotide similarity to HBoV. HBoV2 was found in stool samples from Pakistani children as well as in samples from Edinburgh (1 of the 3 positive samples was derived from a patient >65 years old), indicating that it is not restricted to one region or to young children.
Nine stool samples from dogs suffering from an infectious diarrhea outbreak in Colorado in October 2017 were submitted to IDEXX Reference Laboratories, Inc. (Sacramento, CA, USA) for pathogen testing. Fourteen dogs were involved in the initial outbreak which were identified by clinical signs that started with steatorrhea, progressed to hemorrhagic diarrhea with additional symptoms of lethargy, fever, and low lymphocyte counts pointing to a possible viral infection. At the time of feces collection, the nine sampled dogs were at various stages of the disease, with two of the dogs relapsing a month after initially experiencing parvo-like clinical signs. These stool samples were all negative for Giardia spp., Cryptosporidium spp., Salmonella spp., Clostridium perfringens enterotoxin gene (quantitative), Clostridium perfringens Alpha-toxin gene (quantitative), Canine enteric coronavirus (alphacoronavirus), Canine Parvovirus 2 and Canine Distemper virus using the IDEXX canine diarrhea profile real-time PCR tests.
Feline viral gastroenteritis is considered a common worldwide disease, especially in cats younger than one year of age living in high-density cat environments, such as catteries and shelters. The feline panleukopenia virus (FPV), feline enteric coronavirus (FeCoV), and feline leukemia virus (FeLV) are the most important known viral causes of feline gastrointestinal disease, although various viral agents including astrovirus, adenovirus, rotavirus, and vesiviruses (feline calicivirus, FCV) have been sporadically detected in the stools of cats with enteritis signs by electron microscopy (EM) analysis.
Within the last decade, there has been a resurgence of interest for viral gastroenteritis that was sparked by the identification of novel viruses associated with diarrhea either alone or in mixed infections, occasionally resulting in more severe clinical signs. For many years, viral detection was restricted to a few specialized laboratories with EM equipment, and the etiology of a large portion of viral gastroenteric cases remained unknown. However, the introduction of diagnostic molecular tools mainly based on the use of broadly reactive primers, genus- or family-specific, targeting highly conserved genomic regions, increased the viral detection rate significantly, revealing that additional viruses, may be involved in the feline enteritis disease. Furthermore, in recent years, using the advantages of metagenomic approaches for virus characterization and discovery, an unexpectedly high number of previously unknown viruses were detected in the feces of both healthy and diarrheic cats (Table 1).
Information on the epidemiology and genetic heterogeneity of these newly described viruses are still limited, and it is unclear whether these viruses may play a role as enteric pathogens of cats and to which extent they impact on feline health.
The aim of this review is to provide an update on novel enteric viruses that have most recently been identified in association with enteritis signs in cats, focusing the main attention on feline norovirus, feline kobuvirus, and novel feline parvoviruses.