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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.
About 70% of microbial agents causing outbreaks of emerging infectious diseases in humans originate directly from animals. Among respiratory virus infections, the influenza A viruses H5N1 and H7N9 from avian species, and the severe acute respiratory syndrome coronavirus from bats have caused large epidemics–. Atypical bacterial pathogens causing community-acquired pneumonia include Chlamydophila psittaci from psittacine birds and Coxiella burnetti from livestock and other animals. However, human outbreaks due to zoonotic bacteria associated with the emergence of a novel animal virus in the animal host were not previously documented.
In November 2012, an outbreak of human psittacosis affecting six staff members occurred at the New Territories North Animal Management Centre (NTNAMC) in Hong Kong. The human outbreak was preceded by an outbreak of avian chlamydiosis among the detained Mealy Parrots (Amazona farinose). Although birds in the tropical and sub-tropical areas are commonly infected with C. psittaci, most infected birds are asymptomatic,. Large human outbreaks are rare even among bird handlers. Although co-infection of C. psittaci and viruses has been reported in outbreaks of avian species–, no virus-bacterium co-infection of implicated avian species has ever been reported in outbreaks of human psittacosis. In this study, we sought to investigate viruses that cause avian co-infection, which may have led to this outbreak of psittacosis.
Human microbiologic infections, known as zoonoses, are acquired directly from animals or via arthropods bites and are an increasing public health problem. More than two thirds of emerging human pathogens are of zoonotic origin, and of these, more than 70% originate from wildlife. In novel environments, viruses, particularly RNA viruses, can easily cross the species barrier by mutations, recombinations or reassortments of their genetic material, resulting in the capacity to infect novel hosts. Because of their adaptive abilities, RNA viruses represent more than 70% of the viruses that infect humans. When socio-economic and ecologic changes affect their environment, humans may encounter increased contact with emerging viruses that originate in wild or domestic animals.
Wolfe et al. in 2007 and Karesh et al. in 2012 described different stages in the switch from an animal-specific infectious agent into a human-specific pathogen. The key stage is the transition of a strictly animal-specific infectious agent (originating from wildlife or domestic animals) to exposed human populations, resulting in sporadic human infections (Figure 1). If the pathogen is able to adapt to its human host and acquire the means to accomplish an inter-human transmission, horizontal human-to-human transmission occurs and maintains the viral cycle. Sometimes, an intermediate host, such as a domestic animal, is the link between sylvatic viral circulation and human viral circulation. For example, some human infections originating from bats, such as Nipah, Hendra, SARS and Ebola viral infections, may involve intermediate amplification in hosts such as pigs, horses, civets and primates, respectively (Figure 1). Genetic, biologic, social, political or economic factors may explain a switch in viral host targets. For example, climate changes may influence the geographical repartition of vector arthropods, leading to new areas of the distribution of infectious diseases, like Aedes albopictus and Chikungunya infections in the Mediterranean. Morens et al. listed different key factors that may contribute to the emergence or re-emergence of infectious diseases, such as microbial adaptation to a new environment, biodiversity loss, ecosystem changes that lead to more frequent contact between wildlife and domestic animals or human populations, human demographics and behavior, economic development and land use, international travel and commerce, etc.. These patterns of transmission allow identifying different animals to follow in order to monitor the appearance of new or re-emerging infectious agents before its first detection in the human populations. Therefore, hematophagous arthropods, wildlife and domestic animals may serve as targets for zoonotic and arboviral disease surveillance, particularly because sampling procedures and long-term follow-up studies are more easily performed in these hosts than in humans.
Historically, classic viral detection techniques were based on the intracerebral inoculation of suckling mice or viral isolation in culture and the subsequent observation of cytopathic effects on cell lines. Later, immunologic methods, e.g., seroneutralization or hemaglutination, were used to detect viral antigens in various complex samples. These techniques were based on the isolation of viral agents. With the progresses of molecular biology, polymerase chain reaction (PCR)-based methods became the main techniques for virus discovery and allowed the detection of uncultivable viruses, but these techniques required prior knowledge of closely related viral genomes. Next-Generation Sequencing (NGS) techniques make it possible to sequence all viral genomes in a given sample without previous knowledge about their nature. These techniques, known as viral metagenomics, have allowed the discovery of completely new viral species. Because of their low cost, the use of NGS techniques is exponentially increasing.
The transmission of infections between humans occurs after a pathogen from a wild or domestic animal contacts with exposed human populations. The human exposures may or may not be mediated by the bite of bloodsucking arthropods. Surveillance programs may target wildlife, domestic animals or arthropods for emerging viruses before their adaptation to human hosts.
A case was defined as a staff member working at the NTNAMC who was hospitalized for respiratory tract infection between November 1 and November 30, 2012, and confirmed to have C. psittaci infection by polymerase chain reaction (PCR) and/or a four-fold rise in serum microimmunofluorescent antibody titer against C. psittaci (Focus Diagnostics, Cypress, California, USA).
During the last two decades, scientists have grown increasingly aware that viruses are emerging from the human–animal interface. In order to combat this increasingly complex problem, the One Health approach or initiative has been proposed as a way of working across disciplines to incorporate human, animal, and environmental health. Of particular concern are emerging respiratory virus infections; in a recent seminar given by the National Institute of Health on emerging and re-emerging pathogens, nearly 18% were respiratory viruses (1). Among the recently emerged respiratory pathogens contributing to the high burden of respiratory tract infection-related morbidity and mortality, displayed graphically in Figure 1, are influenza viruses, coronaviruses, enteroviruses (EVs), and adenoviruses (Ads). In this report, we summarize the emerging threat characteristics of these four groups of viruses.
Diarrhea is the second most common cause of death worldwide and accounts for about 8 to 9% of the 5.9 million yearly deaths in children under the age of 5 (1, 2). Most of these deaths occur in Southeast Asia and sub-Saharan Africa (3, 4). The chances of infection with enteric viruses are higher in developing countries than developed countries, probably due to suboptimal sanitation and hygienic conditions and low quality of drinking water, especially in rural areas (5). In Cameroon, a limited number of studies have investigated the prevalence of enteric pathogens as the cause of gastroenteritis in humans. These studies mainly focused on the epidemiology of a limited number of pathogens such as rotavirus, norovirus, and enteroviruses, revealing significant differences in the prevalence of these viruses in different settings and time periods (4, 6, 7). In parts of Cameroon, a high prevalence of several enteric viruses such as enterovirus, norovirus, rotavirus, and adenovirus was found in children and adults (8). Generally in Africa, many episodes of gastroenteritis remain unexplained as no etiological agent is determined (9, 10). A proportion of the unexplained gastroenteritis cases are likely due to other known viruses, for which no tests were performed. However, a part of these gastroenteritis cases could also be caused by novel viral agents.
Transmission of these enteric viruses is predominantly fecal-oral, and humans are constantly exposed to these viruses through various routes (11). One of these routes is zoonosis from reservoirs in wild or domestic animals, either by insect vectors or by exposure to animal droppings or tissues. One rich but, until recently, underappreciated reservoir of emergent viruses is bats. Of the ∼5,500 known terrestrial species of mammals, about 20% are bats (12). Several viruses pathogenic to humans are believed to have originated in bats over the last several years, including severe acute respiratory syndrome (SARS)- and Middle East respiratory syndrome (MERS)-related coronaviruses, as well as filoviruses, such as Ebola and Marburg viruses, or henipaviruses, such as Nipah and Hendra viruses (13–18).
In the Southwest region of Cameroon, bats are hunted and eaten. Such close interactions provide ample opportunity for zoonotic events to occur (19).
Previously, we identified a plethora of known and novel eukaryotic viruses in Cameroonian fruit bats using a viral metagenomics approach, including viruses known to cause gastroenteritis in humans (sapovirus, sapelovirus, and rotaviruses A and H) and those not yet associated with gastroenteritis (bastrovirus and picobirna-like viruses) (20–23). In the current study, we metagenomically screened 221 human fecal samples collected in the same region (where bats are hunted and eaten), to assess (i) if any viruses of animal origin could be identified and (ii) which known human gastrointestinal viruses were present. These fecal samples were collected from children less than a year old to adults of more than 60 years who had gastroenteritis and/or were in contact with bats. Additionally, since the gut virome typically contains both eukaryotic and prokaryotic viruses (phages), of which the latter usually represents the largest fraction of the gut virome, we also analyzed the phageome of these samples.
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.
Approximately two thirds of emerging infectious diseases (EIDs) that affect humans originate from bats, rodents, birds, and other wildlife [1–3]. In many of these reservoir host species, emerging viruses appear to be well adapted, with little or no evidence of clinical disease. However, when these viruses spill over into humans, the effects can sometimes be devastating [4–6]. Previously, our limited knowledge of the viral population and ecological diversity harbored by wildlife have complicated the study of EIDs. Thus, comprehensive understanding of the viral community present in wildlife, as well as the prevalence, genetic diversity, and geographical distribution of these viruses, could be valuable for prevention and control of wildlife-origin EIDs.
The order Rodentia is the largest mammalian order, with 33 families and 2,277 species (~ 43% of all mammal species). They live in close contact with humans and their domestic animals and act as a bond between humans, domestic animals, arthropod vectors (ticks, mites, fleas), and other wildlife [8–10]. This interface with humans has led to the rodent origin of important zoonotic viruses including members of the family Arenaviridae, Hantaviridae, Reoviridae, Togaviridae, Picornaviridae, and Flaviviridae [11–18]. Many of these viruses cause severe disease in humans (e.g., Lassa virus; tick-borne encephalitis virus, TBEV; lymphocytic choriomeningitis virus, LCMV; Sin Nombre virus; Hantaan virus, HTNV; Seoul virus, SEOV; and Puumala virus); have only recently been discovered (e.g., Whitewater Arroyo virus and Lujo virus); or appear to have a wider geographical range than originally thought (e.g., Junin virus, Guanarito virus, Machupo virus, and Sabia virus), suggesting that further viral discovery studies in wild rodent populations may be valuable for public health [8, 11–13, 15, 19–25]. Recent reports of rodent viruses have enabled new hypotheses regarding the evolution of hepaciviruses and the origin of coronaviruses (CoVs) and picornaviruses (PicoVs) such as hepatitis A virus [26–29].
China is a megadiversity country and harbors ~ 200 rodent species from 12 families. To develop baseline data on the origin of existing viral EIDs and identify other potential zoonotic viral reservoir hosts, we have conducted a series of viral surveys from rodents, bats, and other small animals and have simultaneously constructed online viral databases of these animals (DBatVir and DRodVir, http://www.mgc.ac.cn/) since 2010 [31–34]. In the current study, 3,055 small mammal individuals of 55 species from the orders Rodentia, Lagomorpha, and Soricomorpha across China were sampled by pharyngeal and anal swabbing. Virome analysis was then conducted to outline the viral spectrum within these samples. On the basis of virome data, we describe the community, genetics, evolution, and ecological distribution characteristics of viruses and determined whether these features change with their host species and locations. The identification of novel mammal viruses provides new clues in the search for the origin or evolution pattern of human or animal pathogens such as hantaviruses (HVs), arenavirus (AreVs), CoVs, and arteriviruses (ArteVs).
The MAstV-1 species is comprised of HAstV-1–8, and surveillance has revealed that HAstV-1 is the most commonly detected type in children, followed by HAstV-2–5, whereas HAstV-6–8 have been rarely detected. HAstV-4 and HAstV-8 have been associated with infection of older children and longer duration of diarrhea (>7 days). A HAstV-4 strain was also isolated from an infant with fatal meningoencephalitis. Based upon the phylogenetic analysis of the ORF2 region, different lineages within each HAstV type have been proposed; HAstV-1 (HAstV-1a–d) and HAstV-2 (HAstV-2a–d) have been divided into four lineages, whereas HAstV-3 (HAstV-3a–b) and HAstV-4 (HAstV-4a–c) have been classified into two and three lineages, respectively.
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.
Picornaviruses are positive-sense, single-stranded RNA viruses with icosahedral capsids. They infect various animals and human, causing various respiratory, cardiac, hepatic, neurological, mucocutaneous and systemic diseases [1, 2]. Based on genotypic and serological characterization, the family Picornaviridae is currently divided into 29 genera with at least 50 species. Among the various picornaviruses belonging to nine genera that are able to infect humans, poliovirus and human enterovirus A71 are best known for their neurotropism and ability to cause mass epidemics with high morbidities and mortalities [3, 4]. Picornaviruses are also known for their potential for mutations and recombination, which may allow the generation of new variants to emerge [5–10].
Emerging infectious diseases like avian influenza and coronaviruses have highlighted the impact of animal viruses after overcoming the inter-species barrier [11–15]. As a result, there has been growing interest to understand the diversity and evolution of animal and zoonotic viruses. For picornaviruses, numerous novel human and animal picornaviruses have been discovered in the past decade [1, 16–27]. We have also discovered a novel picornavirus, canine picodicistrovirus (CPDV), with two internal ribosome entry site (IRES) elements, which represents a unique feature among Picornaviridae. Moreover, novel picronaviruses were identified in previously unknown animal hosts such as cats, bats and camels [29–31], reflecting our slim knowledge on the diversity and host range of picornaviruses. The discovery and characterization of novel picornaviruses is important for better understanding of their evolution, pathogenicity and emergence potential.
Although rodents can be infected by several picornaviruses, the picornaviral diversity is probably underestimated, given the enormous species diversity of rodents. Moreover, little is known about the pathogenicity of the recently discovered rodent pricornaviruses, such as rodent stool-associated picornavirus (rosavirus) A1, mouse stool-associated picornavirus (mosavirus) A1, Norway rat hunnivirus and rat-borne virus (rabovirus A) [32, 33]. In this report, we explored the diversity of picornaviruses among rodents in China and discovered two potentially novel picornaviruses, “Rosavirus B” and “Rosavirus C”. While rosavirus B was detected in the street rat, Norway rats, rosavirus C was detected in five different wild rat species, suggesting potential interspecies transmission. Their complete genome sequences were determined, which showed that “Rosavirus B” and “Rosavirus C” represent two novel picornavirus species distinct from Rosavirus A. Rosavirus C isolated from cell culture causes multisystemic diseases in a mouse model, with histopathological changes and positive viral antigen expression in lungs and liver of infected mice.
Influenza viruses are RNA viruses that are members of the orthomyxovirus family and classified into four types: A, B, C, and D (2). As shown in Table 1, these four types of viruses are characterized by their immunologically distinct nucleoprotein and matrix protein antigens. Influenza A and B viruses consist of hemagglutinin (HA), which binds a sialic acid receptor, allowing the virus to enter the host cell, and neuraminidase (NA), which cleaves the sialic acid to release the virus. Similarly, influenza C and D viruses contain HA-esterase fusion glycoproteins that also allow for the attachment of viral and cellular membranes. Antigenic shifts (influenza A only) in HA, NA, and the HA-esterase proteins contribute to the generation of novel viral strains. The host range of influenza viruses includes humans, birds, pigs, bats, and other livestock animals such as cattle and goats. The network of the influenza viral transmission is complex with both inter- and intraspecies transmission. As the viruses continue to change in their genetic sequences, ongoing research is imperative in investigating the ecology of these viruses at the human–animal interface to control further spread of infections and prevent the risk of future pandemics.
Increasing morbidity from zoonoses is a significant problem in terms of global health, and they are currently considered exotic in Europe. Zoonoses are infectious or parasitic diseases transmitted by animals to humans (Spahr et al. 2018). These infections as aetiological factors can develop in humans in several ways:
by the digestive tract, where the microorganism gets into the body via infected feed (meat) or water, which is quite often in large-scale farming. Therefore, Escherichia and Salmonella transmission to people occurs mainly through ingestion or frequent contact with infected birds. The above microorganisms can live in the external environment for a long period of time without damage to the pathogenic properties.by skin laceration; a break in the continuity of the skin promotes infection by pathogens of the staphylococci and streptococci families. In addition, the infection is intensified by the release of toxins into the host system.by the respiratory system (by inhalation of dust in which the pathogens are raised); infection occurs through direct contact of a healthy individual with contaminated excretion or through indirect contact (low hygiene at the slaughterhouse) with contaminated faeces and secretion on bird feathers (Hugh-Jones and de Vos 2002).
Humans are more susceptible to zoonoses carried by mammals than birds, and they share more diseases with them. This sharing is due to a higher degree of similarity between the intracellular environment of mammals (to which they belong), rather than birds. Many microorganisms need proper conditions and parameters to determine their host, for example, the presence of its receptor on the surface of the cells. These receptors can serve as a site for attachment and penetration into cells, which provides a pathway for the development of infection. The above situation determines the susceptibility of one animal species to a pathogen and resistance of another species. Vectors, such as insects, are also involved in the transmission of various pathogens, which may have an effect on the immune system. In the case of infecting a human with an avian zoonosis, the course of the disease is usually severe with general life-threatening symptoms. People who have been infected with an avian zoonosis require in-hospital treatment in isolation. Avian zoonoses in humans may end in death or a chronic disease requiring prolonged administration of antibiotics (Hugh-Jones and de Vos 2002).
Hence, the aim of this work is to present the aetiological factors of bird zoonoses, which are currently the most threatening to the European population. In addition, the epidemiological and economic analysis of the above infections in humans is presented. In general, zoonoses from birds can be divided by the type of the infectious agent: bacterial, viral and fungal.
A total of 221 human fecal samples (131 from Kumba and 90 from Lysoka) were collected from two hospitals in the Southwest region of Cameroon, for viral metagenomics screening. From these fecal samples, a total of 63 pools were constituted in categories based on age, bat contact status, and location (see Table S1 in the supplemental material). Illumina sequencing of all the 63 human pools generated in total approximately 708 million raw paired-end (PE) reads (between 4.3 and 53.4 million reads per pool). After trimming, 67% of the reads (471 million) were retained and 86% of these retained trimmed reads (405 million) were annotated using Diamond. Of these, 18% (74 million) could be attributed as viral.
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.
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.
Viruses can be identified by a wide range of techniques, which are mainly based on comparisons with known viruses. Historic methods include electron microscopy, cell culture, inoculation in suckling mice and serology, but these methods have limitations. For example, many viruses cannot be cultivated, excluding the use of cell line isolation and serologic techniques, and can only be characterized by molecular methods. In 2011, Bexfield summarized the different molecular techniques that identify new viruses such as microarray, subtractive hybridization-based and PCR-based methods. Although these techniques have allowed the discovery of many viruses, the prior knowledge of similar viruses is required. Recent advances in sequence-independent PCR-based methods have overcome this limitation, and Sequence-Independent Single Primer Amplification (SISPA), Degenerate Oligonucleotide Primed PCR (DOP-PCR), random PCR and Rolling Circle Amplification (RCA) methods have emerged. The end result of most of these PCR methods is amplified DNA that requires definitive identification by sequencing.
Novel DNA sequencing techniques, known as “Next-Generation Sequencing” (NGS) techniques, are new tools providing high-throughput sequence data with many possible applications in research and diagnostic settings. With the development of different NGS platforms, it is now possible to sequence all viral genomes in a given sample without previous knowledge about their nature with the use of sequence-independent amplification followed by high-throughput sequencing. This combination of techniques, known as viral metagenomics, allows the discovery of completely new viral species within a complex sample and, due to decreasing costs, are nowadays exponentially increasing.
NGS techniques are able to generate a huge number of sequences, ranging from thousands to millions of reads, in only one reaction. In order to fully benefit from this depth of sequencing to identify infectious agents present in a given environment, host DNA/RNA should previously be removed from samples. Preliminary treatments are therefore required prior to nucleic acid amplification and sequencing, mainly based on nucleases treatments and/or viral purification by ultracentrifugation on sucrose, cesium chloride or glycerol gradients. These strategies are known as “Particle-Associated nucleic acid amplification”, i.e., they try to isolate intact (i.e., infectious) viral particles from their environment, protected from the action of nucleases. Subsequent low amount of nucleic acids have required the use of Sequence-Independent Amplifications (SIA) such as SISPA, DOP-PCR, random PCR, RCA. Although these techniques allow generating enough nucleic acid material for sequencing, their main disadvantage remains that they distort quantitative analyzes by introducing bias of amplification in viral diversity studies. As a consequence, quantitative analyses of the composition of resulting viromes may not reflect the reality.
In diagnostic virology, in either human or veterinary medicine, viral metagenomics has allowed the discovery of causative viral agents of disease conditions. Virome analyses have also been conducted to describe the baseline viral diversity in healthy human conditions, as a prior knowledge before studying the viral flora of pathologic conditions.
In the same way, the use of viral metagenomics as a tool for arboviral and zoonotic disease surveillance requires prior knowledge of the viral diversity associated to hematophagous arthropods and animals in close contact with humans. This review thus summarizes our current knowledge of the diversity of viral communities associated with several arthropods, wildlife and domestic animals and present its potential applications for the surveillance of zoonotic and arboviral diseases.
West Nile virus is the etiological agent of an emerging zoonotic disease whose impact on animal and public health is considerable, being the most widespread arbovirus in the world today (reviewed in Hayes et al., 2005a; Kramer et al., 2008; Brault, 2009). A percentage of WNV infections result in severe encephalitis, and it is a communicable disease both for human and animal health. WNV taxonomically belongs to the family Flaviviridae, genus Flavivirus. Virions are spherical in shape, about 50 nm in diameter, and consist of a lipid bilayer that surrounds a nucleocapsid that in turn encloses the genome, a unique single-stranded RNA molecule, which encodes a polyprotein that is processed to give the 10 viral proteins. Of them, three (C, E, and M) form part of the structure of the virion, and the rest (NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5) are so-called “non-structural” and play important roles in the intracellular processes of replication, morphogenesis, and virus assembly. Inserted into the lipid bilayer are two proteins, E (from “envelope”) and M (“matrix”), which participate in important biological properties of the virus, such as its host range, tissue tropism, replication, assembly, and stimulation of cellular and humoral immune responses. E protein contains the major antigenic determinants of the virus.
As far as we know, there are no serotypes of WNV, but two main genetic variants or lineages can be distinguished, namely lineages 1 and 2. While the former is widely distributed in Europe, Africa, America, Asia, and Oceania, the second is found mostly restricted to Africa and Madagascar, although it has recently been introduced in Central and Eastern Europe (Bakonyi et al., 2006; Platonov et al., 2008) and has further extended to southern Europe (Bagnarelli et al., 2011; Papa et al., 2011). In addition, other viral variants closely related phylogenetically to WNV have been described, which are different from lineages 1 and 2, and have been proposed as additional WNV lineages. One of them, known as “Rabensburg virus,” isolated form mosquitoes in the Czech Republic in 1997, shows low pathogenicity in mice (Bakonyi et al., 2005). Similarly, other viruses closely related to WNV have been isolated in India (Bondre et al., 2007), Russia (Lvov et al., 2004) Malaysia (Scherret et al., 2001), and Spain (Vazquez et al., 2010). All these viruses have been proposed to represent different genetic lineages of WNV. Except for the Indian variant, which has been involved in outbreaks of encephalitis in humans, the rest are of unknown relevance for animal and human health.
West Nile fever/encephalitis is a disease transmitted mainly by mosquitoes, while wild birds are its natural reservoir. WNV is capable of infecting a wide range of bird species. Nevertheless, birds were considered less susceptible to the disease until the recent epidemic of WNV in North America, affecting many species of birds lethally, made to re-examine this concept (Komar et al., 2003). Occasionally it may affect poultry species, mainly geese and ostriches. Other domestic birds like chickens and pigeons, are susceptible to infection but do not get sick, and are often used as sentinels for disease surveillance. In addition to birds, WNV can also affect a wide range of vertebrates species, including amphibians, reptiles, and mammals, and it is particularly pathogenic in humans and horses, which act epidemiologically as “dead end hosts,” that is, they are susceptible to infection but do not transmit the virus (McLean et al., 2002; Kramer et al., 2008).
The first case of WNF was described in Uganda (West Nile district, hence the name of the virus) in a feverish woman, from whose blood the virus was first isolated in 1937 (Smithburn et al., 1940). It was considered a mild disease, endemic in parts of Africa (an “African fever”). However, since around 1950s, the occurrence of disease outbreaks with neurological disease, lethal in some cases, caused by WNV, especially in the Middle East and North Africa, made necessary to rethink this concept. In humans, the majority of WNV infections are asymptomatic, about 20% may develop mild symptoms such as headache, fever, and muscle pain, and less than 1% develop more severe disease, characterized by neurological symptoms, including encephalitis, meningitis, flaccid paralysis, and occasionally severe muscle weakness (Hayes et al., 2005b). Advanced age is considered a risk factor for developing severe WNV infection or death. The mortality rate calculated for the recent epidemic of the disease in the U.S. is 1 in every 24 human cases diagnosed (Kramer et al., 2008).
In horses (reviewed in Castillo-Olivares and Wood, 2004) neurological disease is manifested by approximately 10% of infections, and is mainly characterized by muscle weakness, ataxia, paresis, and paralysis of the limbs, as a result of nerve damage in the spinal cord. They may also suffer from fever and anorexia, tremors and muscle stiffness, facial nerve palsy, paresis of the tongue, and dysphagia, as a result of affection of the cranial nerves. A proportion of horses infected with WNV die spontaneously or is slaughtered to avoid excessive suffering. The mortality rate can vary between outbreaks. For example, in the outbreak in 2000 in the Camargue (France), 76 horses were affected, of which 21 died (Zeller and Schuffenecker, 2004). In 1996 in Morocco, a WNV outbreak affected 94 horses, of which 42 died (Zeller and Schuffenecker, 2004). Severe equine cases do not seem to predominate in older horses, as occurs in humans (Castillo-Olivares and Wood, 2004). Other mammals may also suffer from the disease. Rodents such as laboratory mice and hamsters are highly susceptible, so they can be used as experimental model of WNV encephalitis. Lemurs and certain types of squirrels appear to be the only mammals capable of maintaining the virus in local circulation (Rodhain et al., 1985; Root et al., 2006). WNV can also infect other mammals, including sheep, in which it causes abortions, but rarely encephalitis (Hubalek and Halouzka, 1999). WNV has been isolated from camels, cows, and dogs in enzootic foci (Hubalek and Halouzka, 1999). The virus has been shown to infect frogs (Rana ridibunda), which in turn are bitten by mosquitoes, so that the existence of an enzootic cycle in these amphibians is postulated, at least for some variants of the virus (Kostiukov et al., 1986). Outbreaks of severe WNF with high mortality have been reported in captive alligators and crocodiles, presumably transmitted through feeding of contaminated meat (Miller et al., 2003). It has been shown experimentally that WNV can infect asymptomatically pigs (Teehee et al., 2005) and dogs (Blackburn et al., 1989; Austgen et al., 2004). However, guinea pigs, rabbits, and adult rats are resistant to infection with WNV (McLean et al., 2002). Among non-human primates, rhesus and bonnet monkeys (but not Cynomolgus macaques and chimpanzees), inoculated with WNV develop fever, ataxia, prostration with occasional encephalitis and tremor in the limbs, paresis or paralysis. The infection can be fatal in these animals.
The virus is propagated in the reservoir hosts, resulting in a viremic phase that usually lasts no more than 5–7 days (Komar et al., 2003). The duration and level of viremia depends on the species infected (Komar et al., 2003). The detection of the virus or its genetic material in serum or cerebrospinal fluid in a laboratory test is a proof of diagnostic value (De Filette et al., 2012). The virus is evidenced by virological (virus isolation) or molecular (RT-PCR-conventional and real-time, NASBA) techniques. In epidemiological surveillance it is useful to detect the presence of WNV in mosquitoes, for which they are homogenized and analyzed using the same methods mentioned above (Trevejo and Eidson, 2008). Specific antibodies against the virus are detectable in blood few days after infection (Komar et al., 2003; De Filette et al., 2012). Antibody detection is performed by serological tests (enzyme immunoassay or ELISA, hemagglutination inhibition or HIT) which can be confirmed by more specific serological techniques (virus-neutralization test; Sotelo et al., 2011c). Serological diagnosis of acute infection should be done by detection of IgM antibodies in serum and/or cerebrospinal fluid using an immunocapture ELISA together with the detection of an increase in antibody titer in paired sera taken one in the acute phase and the other, at least 2 weeks later (Beaty et al., 1989).
The fight against this disease is not straightforward because there are no vaccines licensed for human use, and even though there are some available for veterinary use, they are efficacious to prevent disease symptoms and outcome at the individual level but do not prevent the spread of the infection, mainly due to the establishment of an enzootic cycle among wild birds and mosquitoes (Kramer et al., 2008; De Filette et al., 2012). Control methods are mainly based on prevention and early detection of virus spread through epidemiological surveillance and targeted application of insecticides and larvicides (Kramer et al., 2008).
Astroviruses are classified within the unassigned Astroviridae family and are non-enveloped viruses characterized by a positive sense, single-stranded RNA (ssRNA) genome 6.4–7.9 kb long comprised of a 5′-untranslated region (UTR), three open reading frames (ORFs)—ORF1a, ORF1b, and ORF2, a 3′-UTR, and a poly A tail. The ORF1a region encodes a non-structural polyprotein (serine protease), ORF1b encodes a polyprotein including the RNA-dependent RNA polymerase (RdRp), and ORF2 encodes the viral capsid protein. A further ORF, termed ORFX, has been observed in classic HAstVs and some mammalian astroviurses, overlapping the 5′ end of ORF2 which may be translated through a leaking scanning mechanism. Astroviruses exhibit several distinctive features in addition to a distinctive morphology. The viruses lack a RNA-helicase domain encoded within the genome and utilize a ribosomal frameshifting mechanism to translate the RdRp, which distinguishes the Astroviridae family from other non-enveloped ssRNA virus families such as Picornaviridae and Caliciviridae. The greatest diversity in the genome is within the ORF2 region, which is characterized by a highly-conserved N-terminal domain (amino acids (aa) 1–424), a hypervariable domain (aa 425–688) which is believed to form the capsid spike and contribute to receptor binding, and a highly acidic C-terminal domain.
The duck (Anas platyrhynchos) is one of the economically important poultry species as a source of meat, eggs and feathers. Ducks harbour most of the hemagglutinin (HA) and neuraminidase (NA) subtypes of avian influenza viruses that are currently known [2, 3] and serve as the principal natural reservoir host for influenza A viruses [2, 4–6]. Influenza A viruses maintained in wild aquatic birds have been associated with stable host switch events to novel hosts including mammals and domestic gallinaceous poultry leading to the emergence of novel influenza A viruses [7, 8].
To control the outbreaks of emerging or re-emerging viral diseases and prevent the transmission of viruses from the reservoir host, monitoring the virome status in the reservoir hosts is essential. Further, understanding the viral diversity in the poultry gut will improve the knowledge of enteric disease syndromes and the feed conversion efficiency of the poultry species. In recent years, next generation sequencing technology based viral metagenomics has provided a powerful tool for large-scale detection of known and unknown viruses existing in the reservoir host [11, 12]. Using this approach, known and novel viruses have been characterized from the enteric tract of turkey, bats, pigs, rodents, pigeon, ducks and ferrets. To obtain an unbiased measure of the viral diversity in the enteric tract of ducks, we deep sequenced viral nucleic acid isolated from cloacal swabs of 23 ducks collected from Bhoj wetland of Bhopal, the capital of the central Indian state of Madhya Pradesh. The present study revealed that the duck gut virome contained sequences related to a wide range of animal, insect, plant, and bacterial viruses. This study increases our understanding of the viral diversity present in the enteric tract of ducks. Further, this virome dataset provide a baseline faecal virome of the ducks and will be used as reference for identification of future changes in its virome composition, which may be associated with disease outbreaks or environmental changes.
Infectious disease can be viewed as a play involving at least two characters: the pathogen and the host. While both roles can be represented by a great variety of performers, pathogens exhibit by far the highest variety and complexity. This review is about viral infections in animals. It aims first to give an idea of the enormous complexity and diversity of the existing infectious agents, emphasizing their extraordinary capacity for change and adaptation, which eventually leads to the emergence of new infectious diseases. Secondly, it focuses on the influence of the environment in this process, and on how environmental (including climate) changes occurring in recent times, have precise effects on the emergence and evolution of infectious diseases, some of which will be illustrated with specific examples. Finally, it describes the recent and dramatic expansion of two of the most important emerging animal viral diseases at present, bluetongue (BT) and West Nile fever/encephalitis (WNF), dealing with their relationship to climate and other environmental changes, particularly those linked to human activities, collectively known as “global change,” and that can be at least in part seen a consequence of the “globalization” phenomenon.
Four distinct papillomavirus sequences were identified in two bat species, E. helvum (Eidolon helvum papillomavirus 8; EhPv-8) and T. perforatus (T. perforatus papillomavirus 1, 2 and 3; TpPv-1, -2, -3). Complete coding sequences were recovered for EhPv-8 (acc. no. KX434763, 6985 bp), TpPv-1 (acc. no. KX434764, 7180 bp) and TpPv-3 (acc. no. KX434767, 7083bp). EpPv-8 shared 63% aa similarity to E. helvum papillomavirus type 1 across the DNA helicase protein (E1). TpPv-1, TpPv-2, and TpPv-3 (acc. no. KX434766, partial genome) shared 44%, 47% and 44% aa similarity across the E1 protein with human papillomavirus 63, Miniopterus schrebersii papillomavirus 1, and Castor canadensis papillomavirus 1, respectively (Fig 7).
The most pest-prone species of poultry are primarily hens, quail and turkeys. The condition is caused by a virus belonging to the Herpesvirus genus. The way they penetrate the organism is through the respiratory system or gastrointestinal tract. Infection usually occurs immediately after hatching. The virus contained in the exfoliated warts of the pen still retains its virulence for more than 12 months after initiation. Infected birds show weight loss and paroxysmal symptoms. However, it often occurs that the course of this disease is very violent and no clinical symptoms were observed in humans (Ryan and Ray 2004; Koelle and Corey 2008; Johnston et al. 2011; Schiffer et al. 2014).
Next, all of the above findings were considered in conjunction with the literature data on the transmission ecology collated for each of the 36 viruses in Figure S1a. Pieced together on this basis was an outer- to inner-body line-up of viruses by organ system or combination of organ systems, guided by the one-to-four virus infiltration score, the corresponding virus organ system tropism, the matching virus transmission modes, length of the infection and shedding periods, infection severity level, and virus environmental survival rate, see Figure 3 and, also, Figure S1d.
The emergence of novel infectious diseases continues to represent a threat to global public health. Emerging pathogens have been defined as those newly recognised infections of humans following zoonotic transmission or those increasing in incidence and/or geographic range. High-profile examples of emerging pathogens include the discovery of the novel Middle East respiratory syndrome (MERS) coronavirus from cases of respiratory illness in 2012 and the expansion of the range of Zika virus across the South Pacific and the Americas. The emergence of previously unseen viruses means that the set of known human viruses continually increases by around two species per year. Initial comparative studies identified trends among emerging human pathogens, e.g., increased risk of emergence for pathogens with broad host ranges and RNA viruses [6–9]. However, more recent comparative analyses have focused on risk factors for specific pathogen traits such as transmissibility [10–12]. Here, we focus on understanding the ecological determinants of pathogen virulence, using all currently recognised human RNA viruses as a study system.
Emerging RNA viruses vary widely in their virulence, with some never having been associated with human disease at all. For example, Zaire ebolavirus causes severe haemorrhagic fever with outbreaks, including the 2014 West African outbreak, showing case fatality ratios (CFRs) of approximately 60% or more. In contrast, human infections with Reston ebolavirus have never exhibited any evidence of disease symptoms. Applying the comparative approach to understand the ecology of virulence could offer valuable synergy with studies of emergence towards prioritisation and preparedness in the detection of potential new human viruses.
Few comparative analyses have addressed the risk factors driving human pathogen virulence to date (but see [17–19]), and none have investigated virulence across the entire breadth of currently recognised human RNA viruses. Of relevance here is an ongoing, largely theoretical debate about the possibility of an evolutionary tradeoff between virulence and transmissibility, which has proven challenging to empirically characterise [20–22]. We also note that in the absence of coevolution, a zoonotic virus may demonstrate ‘coincidental’, nonadapted virulence. We therefore compared viruses with different levels of transmissibility in human populations. Transmission route is another potential predictor of virulence; higher mortality rates have been observed in earlier comparative analyses for vector-borne pathogens and pathogens with greater environmental persistence. We therefore hypothesised vector-borne transmission or routes with environmental components (e.g., faecal–oral or food-borne transmission) would be associated with higher virulence than direct, contact-based transmission.
Several studies have suggested a link between host range breadth and virulence, in which higher virulence has been predicted for pathogens with a narrower, specialist host range. Virulence (or host exploitation) has also been predicted to vary with host relatedness through phylogenetic distance or in phylogenetic clustering. We therefore hypothesised that a narrow host range, and specifically, infection of nonhuman primate hosts, may also predict virulence. Finally, we hypothesised that a broader tissue tropism could predict higher virulence. This idea is largely unexplored, although experimental studies have demonstrated a broader tissue tropism for more virulent strains of Newcastle disease virus.
We aimed to determine patterns of virulence across the breadth of all known human RNA viruses. We then aimed to use predictive machine learning models to ask whether ecological traits of viruses can act as predictive risk factors for virulence in humans. Specifically, we examined hypotheses that viruses would be more highly virulent if they lacked transmissibility within humans, had vector-borne or faecal–oral transmission routes, had a narrow host range or infected nonhuman primates, or had greater breadth of tissue tropisms.