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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.
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.
Although viruses infecting humans had already been described since 1901 and viruses were suspected to play a role in diarrhea, it lasted until 1972, when the first virus causing gastroenteritis (norovirus) was identified in an outbreak of diarrhea in Norwalk (California, United States). Shortly after the discovery of norovirus several other viruses causing gastroenteritis were discovered: rotavirus in epithelial cells of children with gastroenteritis, astrovirus in infantile diarrhea cases, enteric adenoviruses in the feces of children with acute diarrhea, and sapovirus during an outbreak of gastroenteritis in an orphanage in Sapporo, Japan. All these viruses spread via the fecal-oral route through person-to-person transmission and are described in more detail below.
Noroviruses are part of the family Caliciviridae and outbreaks of norovirus gastroenteritis have been reported in cruise ships, health care settings, schools, and in the military, but norovirus is also responsible for around 60% of all sporadic diarrhea cases (diarrhea cases where an enteropathogen could be found), reviewed in the literature. The pathogenesis of norovirus infection has been tested in vivo. Filtrated norovirus was given to healthy volunteers after which most of them developed diarrhea. Culturing of the virus, however, has been a problem since its discovery, yet one study has recently described the cultivation of norovirus in B cells, and has revealed that co-factors, such as histo-blood antigen expressing enteric bacteria, are probably needed before enteric viruses can be cultured in vitro. Sapoviruses are also members of the Caliciviridae. There are five human genogroups of sapovirus described which account for 2.2%–12.7% of all gastroenteritis cases around the globe. Sapovirus outbreaks occur throughout the year and can be foodborne. For sapoviruses it has been described that the virus was not found before onset of an outbreak, and that it was found in 95% of the patients during an outbreak, while it declined to 50% after an outbreak, indicating that the virus introduces disease in a naturally infected host.
Rotavirus infection is the most common cause of viral gastroenteritis among children; however, parents of infected children also often become ill and as a result rotavirus is the second most common cause of gastroenteritis in adults. Studies in human volunteers have shown that infection with rotavirus causes diarrhea, results in shedding of the virus and a rise in antibody anti-virus titer after infection. Additionally, astroviruses infections are common, accounting for about 10% of all sporadic diarrhea cases. Astrovirus has been isolated from diseased people, filtrated and administered to healthy individuals after which in some of the volunteers diarrheal disease was observed and astrovirus was shed in their stools. The virus can replicate in human embryonic kidney cells and was detected by electron microscopy (EM). Adenoviruses are responsible for around 1.5%–5.4% of the diarrhea cases in children under the age of 2 years, reviewed in the literature. Of the 57 identified adenovirus types, only adenoviruses type 40 and 41 are associated with diarrhea. Next to these two types, adenovirus type 52 can also cause gastroenteritis, although it has been argued whether type 52 is actually a separate type since there is not sufficient distance to adenovirus type 41. Adenoviruses can generally be propagated in cell lines; however, enteric adenovirus 40/41 are difficult to culture, reviewed in the literature.
West Nile virus (WNV) is a positive-sense single-stranded ribonucleic acid (RNA) virus in the Flaviviridae family. WNV is the leading cause of mosquito-borne encephalitis in humans in many parts of the world. In addition to humans, many animals are also susceptible to WNV infections. Large outbreaks have occurred globally in both humans and other animals, such as horses and pigs. Birds are the natural reservoirs of WNV. Bird-to-bird, bird-to-mammal and bird-to-human transmissions are achieved by mosquito bites, with humans and other mammals serving as dead-end hosts because of low viral loads.
Camels are one of the most unique mammals on earth and have shown perfect adaptation to desert life. There are two surviving old-world camel species: Camelus dromedarius (dromedary or one-humped camel), which inhabits the Middle East and North and Northeast Africa, and Camelus bactrianus (Bactrian or two-humped camel), which inhabits Central Asia. Among the 20 million camels on earth, 90% are dromedaries. Although WNV is known to infect some of the new world camels, such as llamas and alpacas,1 only antibodies against WNV have been detected in the sera of old-world camels, such as the dromedaries in the Middle East, North Africa and Spain, with a seroprevalence of 3%–38%.2, 3, 4, 5 To date, no WNV has been isolated or amplified from either dromedary or Bactrian camels. Recently, the emergence of Middle East respiratory syndrome (MERS) and the isolation of the MERS coronavirus (MERS-CoV) from dromedaries boosted interest in the search for novel viruses in dromedaries.6, 7, 8, 9, 10, 11, 12, 13 In this article, we report the first isolation of WNV from a dromedary calf in the United Arab Emirates during the process of MERS-CoV screening and the results of the comparative genome and phylogenetic analysis.
In the 1980s and 1990s some viral agents were identified for which the direct association with disease is less clear. Aichi viruses are members of the Picornaviridae identified in fecal samples of patients with gastroenteritis. Aichi virus infection has been shown to elicit an immune response. Since their discovery, two case-control studies were performed, but, although both studies only found Aichi virus in stools of diarrheic patients, the prevalence of Aichi virus (0.5% and 1.8%) was too low to find a significant association with diarrhea. In immuno-compromised hosts the virus is found in higher quantities and is not associated with diarrhea. Toroviruses, part of the Coronaviridae, were first identified in 1984 in stools of children and adults with gastroenteritis. Torovirus infection is associated with diarrhea and is more frequently observed in immuno-compromised patients and in nosocomial infected individuals. Retrospective analysis of nosocomial viral gastroenteritis in a pediatric hospital revealed that in 67% of the cases torovirus could be detected. However, only a limited number of studies report the detection of torovirus and therefore the true pathogenesis and prevalence of this virus remains elusive. Picobirnaviruses belong to the Picobirnaviridae and were first detected in the feces of children with gastroenteritis. Since the initial discovery, the virus has been detected in fecal samples of several animal species, and it has been shown that the viruses are genetically highly diverse without a clear species clustering, reviewed in the literature. This high sequence diversity has also been observed within particular outbreaks of gastroenteritis, limiting the likelihood that picobirnaviruses are actually causing outbreaks, as no distinct single source of infection can be identified.
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.
HAstVs are a classic cause of viral diarrhea in children, along with rotavirus, norovirus, sapovirus and adenovirus. Seroprevalence studies indicate that most children in Europe encounter astrovirus before the age of two. Astrovirus-associated diarrhea is not reported in immunocompetent adults, as infection in childhood is considered to confer protective immunity. Additionally, humoral immunity is considered to play a major protective role, along with cellular adaptive immunity. Therefore, immunosuppressed patients and the elderly can also develop astrovirus-associated diarrhea.
In non-immunocompromised individuals, after an incubation period of 4–5 days, an astrovirus infection will induce a mild disease, characterized by mild and short watery diarrhea for two to three days, followed by nausea, vomiting, and abdominal pain, which usually resolves spontaneously. These symptoms are most often milder than a rotavirus infection. Recent seroprevalence studies have indicated that some infections can be asymptomatic as well. As reported for rotavirus and norovirus, astrovirus has also been associated with intussusception in infants. Although virological diagnosis of astrovirus-associated diarrhea is not routinely used in medical practice, it is sometimes used in epidemiological studies in the context of diarrheal outbreaks and surveillance of diarrheal diseases.
An astrovirus infection in immunocompromised individuals may induce gastroenteritis, but it can also lead to severe and sometimes fatal systemic and central nervous system (CNS) infections, as seen in multiple cases of astrovirus-associated encephalitis and meningitis. These reports are associated with newly identified HAstVs that belong to novel species (MAstV 6 and 9). Studies are under way to assess the actual disease burden associated with these novel neurotropic astroviruses in humans. These novel astroviruses are enteric viruses, associated with diarrhea and fecal carriage, but their pathogenicity in the non-immunosuppressed host has not yet been precisely determined, although a case of meningitis in an apparently healthy adult has recently been reported. Therefore, these newly-discovered viruses seem to share some clinical characteristics with enteroviruses, due to their association with diarrhea, but may also induce meningitis and encephalitis in the immunosuppressed patients. For this reason, their detection should now be part of the laboratory diagnostic work-up in patients, in particular those who are immunosuppressed and are diagnosed with meningitis or encephalitis of unknown cause.
In mammals, astroviruses have been reported in piglets, minks and dogs with preweaning diarrhea, but accurate diagnosis is complicated due to the prevalence of fecal shedding in healthy animals, which complicates the interpretation of the results. Therefore, etiological diagnostic is not a routine practice. In mink presenting with the so called “shaking mink syndrome”, and cattle with encephalitis, astroviruses can be tested in necropsy brain samples. Additionally, astroviruses have been associated with severe avian diseases (i.e., chicken diarrhea, duck hepatitis, turkey enteritis, and avian nephritis), and diagnosis can be made in severely affected flocks by reverse transcription polymerase chain reaction (RT-PCR), using necropsy samples in specialized laboratories.
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.
In 1975, the first observation by EM of 28–30 nm particles was reported in the stool of babies with gastroenteritis. The star-shaped surface configuration of the viruses rapidly led the author to propose the name of “astrovirus” (derived from the Greek “astron” which means “star”) and, since then, this morphological characteristic has been widely used for the detection of astrovirus infection in both humans and animals. Direct EM is complicated by the fact that only a minority of virions exhibit a complete star-shaped structure, and careful searching may be necessary to distinguish between, for example, astrovirus and calicivirus, which are similar in size. Sensitivity of EM is also dependent on elevated concentrations of particles, usually around 107 per gram of stool. The use of immune electron microscopy (IEM) techniques using specific antibodies or convalescent sera can improve the sensitivity of the detection and help with the typing or the detection of new viral agents. Due to the limitations described above, the use of EM for the diagnosis of viral infections has been superseded by molecular methods, and therefore, it is rarely available or used in clinical laboratories anymore.
Avian astroviruses belong to the genus Avastrovirus of the Astroviridae family. The viral particles are small, non-enveloped, positive sense RNA viruses, 28 to 30nm in diameter, and have a star-like morphology (21). Turkey Astrovirus type 1 (TAstV-1) was first described in 1980 by McNulty et al. (22) in the United Kingdom, and the first isolated of TAstV in the United States was identified in 1985 (15). A second TAstV type, which was antigenically and genetically distinct from the previously identified as TAstV-1, was isolated 1996 and designated as TAstV-2 (13,31,32). The entire genome sequence of the TAstV-2 isolate, NC/96, has been reported and bears many similar features to Human Astrovirus (HAstV) (15). Moreover, astroviruses are linked with enteric disease in humans and young animals such as calves, lambs, pigs, dogs, cats and minks (15,21). The most important infectious disease caused by TAstV are the enteric diseases affecting the digestive tract of commercial poults proposed to result in more economic loss than those affecting any other system reported worldwide, including Brazil (16,17,26,27,28,30,34,35). In addition, no vaccine currently exists for the enteric disease caused by astroviruses, which leads the disease to the bio-security manners to control virus infection and spread (15).
Turkey Coronavirus (TCoV) was described affecting commercial poults in Brazil, suspected of suffer from PEMS-Poult Enteric Mortality Syndrome (34,35). In addition, coronaviruses had often been described as being fastidious. This claim arose from the difficulty that virologists had experienced in finding types of cells in which grow coronaviruses in vitro (7,11). Moreover, the TCoV was confirmed as being in the UK in 2001 (6) and has being demonstrated as worldwide distribution (7).
Alternatives to diagnosis both TAstV-2 and TCoV, and also others viruses, has been applied in order to overcome virus isolation (5). In this way, molecular approaches seems to be more appropriated to direct detect viral RNA from clinical samples, by the use conventional and/or alternative reverse transcriptase polymerase chain reaction - RT-PCR (1,5,8,14,18,24,25,29). Since both viruses have been associated to PEMS outbreak in North America (1,2,13,18,22,23,24,27,29) and recently UK and Wales (9), few works describe TCoV and TAstV-2 epidemiology among Brazilian’s producers.
The aim of this study was to verify viral RNA from TCoV and TAstV-2 from 30-day-old affected poults, presenting clinical signs of PEMS. For this purpose, both simplex and multiplex RT-PCR assays were applied to detect viral RNA from different clinical samples at different year seasons.
Interest in the virome, or the entire population of viruses present in a biological sample, has increased recently due to improved availability of high throughput sequencing or next generation sequencing (NGS) technologies, and improved metagenomic analytical methods [1, 2]. The virome comprises all types of viruses, including those that infect prokaryotic and eukaryotic organisms, DNA or RNA viruses, and viruses that cause acute or chronic infections. Many of these viruses are difficult or impossible to propagate in cell culture, and molecular detection is difficult as no common gene such as the ribosomal 16S gene that is present in bacterial species exists in viruses. These limitations have hindered the identification and characterisation of uncultured viruses [3, 4]. Recently, due to the advent of molecular enrichment protocols, high throughput sequencing and new metagenomic analytical methods we are now able to explore, identify and characterise viruses from different biological and environmental samples with a greater capacity [2, 5–11]
In studies of human faeces, the virome has been shown to include viruses that infect eukaryotic organisms and viruses that infect prokaryotes (bacteriophages) [2, 5, 12–18]. Bacteriophages have been reported in many studies to be the most frequently detected viral constituent in the gut of humans [1, 2, 5, 8, 16, 19, 20]. The faecal virome has been characterised for several animal species including pigs, bats, cats, pigeons, horses and ferrets [2, 6, 7, 9–11, 21–31]. In dogs, the presence of enteric viral pathogens such as canine parvovirus, coronavirus, rotavirus and distemper virus (Paramyxoviridae) have been identified only through targeted studies [32–35]. To date, only one published study has used high throughput sequencing to investigate the faecal viral population in diarrhoeic dogs. These investigators analysed faeces from dogs with acute diarrhoea and detected two new virus species, canine sapovirus and canine kobuvirus; known canine enteric viruses such as canine coronavirus, canine parvovirus, canine rotavirus as well as plant and insect viruses were also reported.
The aim of this study was to describe the faecal virome of samples collected from healthy dogs, and compare these findings to the faecal virome of dogs with acute diarrhoea in Australia, using an Illumina MiSeq shotgun metagenomic sequencing approach.
Gastrointestinal (GI) symptoms are not an uncommon manifestation of an influenza virus infection. However, little is known about the GI pathogenesis of influenza viruses. It is possible that GI symptoms developed during the clinical course of influenza could either be a part of disease manifestation, due to the side effects of antibiotic treatment, or a co-infection with other diarrheal pathogens. Gastrointestinal manifestation associated with seasonal influenza has been recognised for more than 30 years. During the influenza A epidemic of 1988 in Australia several children developed hemorrhagic gastritis of varying severity after a typical Influenza-like illness (ILI). Similarly, during the two epidemics in 1973 and 1974, influenza virus B was detected in hospitalised children who had abdominal pain, often severe enough to require differentiation from acute appendicitis, as a dominant symptom. Less severe GI symptoms have been reported to occur in 20-30% of children with an influenza B infection. Early epidemiologic study of the pandemic influenza A/H1N1 2009 virus suggested that it produced diarrhea, vomiting, or both, in ≈ 25% of case-patients.
However, fecal excretion of pandemic and seasonal influenza viruses has rarely been studied, and the lack of reports of co-infection among influenza and enteric viruses is probably because of reporting bias. Consequently it remains unknown whether co-infection with influenza pathogens in patients with GI symptoms represents rare events. Previous studies reported the detection of seasonal influenza in the stools of pediatric patients presenting concurrent acute diarrhea (AD) and ILI, and in the stools of hospitalised and outpatients presenting both GI and respiratory symptoms. Influenza viral RNA was also detected in the stools of A/H1N1 2009 positive patients hospitalised due to the progression of acute gastroenteritis. Previous studies showed that the avian influenza A/H5N1 virus can be detected in stools, and the presence of this virus was further demonstrated in the biopsy of the small and large intestines of fatal cases. Other respiratory viruses have been found in stools, such as respiratory syncytial virus, SARS coronavirus, adenovirus and bocavirus. But, to our knowledge, there are no studies reporting the detection of Influenza viruses in the stools of adult patients consulting in general practice for acute diarrhea.
In the present study we aimed to investigate the presence of pandemic and seasonal influenza viruses in the stools of General Practitioners’ (GPs) adult patients presenting exclusively GI symptoms and the proportion of concurrent infections by enteric and influenza viruses by using a case control design.
Newcastle disease virus (NDV), synonymous with Avian avulavirus 1, is a negative-sense single-stranded RNA virus that belongs to the genus Avulavirus of the Paramyxoviridae family. It is an avian virus causing high morbidities and mortalities in most species of wild and domestic birds globally and is associated with major economic loss in poultry farms worldwide. Transmission of the virus occurs through exposure to the fecal materials and other excretions of infected birds or contaminated food, water and equipment. In birds, NDV mainly causes diseases in the respiratory, neurological, and gastrointestinal systems. Occasionally, NDV has also caused infections in mammals, such as cattle, sheep, and mink. In 1952, NDV was isolated from the lung of a six-month-old calf with pneumonia in the United States. In 2012, it was isolated from the blood of two apparently healthy sheep in India. In 2017, it was isolated from an outbreak of hemorrhagic encephalitis and pneumonia in domestic mink from mainland China. For humans, exposure to infected birds can cause mild self-limiting conjunctivitis and influenza-like symptoms.
The NDV genome comprises a single-stranded negative sense RNA that encodes for a nucleocapsid protein (N), a phosphoprotein (P), a matrix protein (M), a fusion protein (F), a hemagglutinin-neuraminidase protein (HN), and a large polymerase protein (L), from the 3′ terminus to the 5′ terminus. Based on the complete coding sequence of the F protein, NDV strains are classified into class I and class II, with class II NDVs being more diverse, and are further classified into genotypes I to XVIII. In terms of pathogenicity, NDVs can be categorized into velogenic (virulent), mesogenic (intermediate), or lentogenic (non-virulent), which have been linked to their virulence in chickens or the presence of conserved amino acids in the F and HN proteins which are known to be involved in pathogenesis of NDV infection, such as virus attachment, host-cell membrane fusion, virus dissemination, and F protein activation.
Although NDV is known to infect some mammalian species, it has never been isolated or amplified from camels. However, a previous study reported that a pigeon NDV isolate was able to agglutinate camel red blood cells, achieving haemagglutination titer comparable to the level obtained with chicken red blood cells. This suggested that haemagglutination protein binding receptor was also present on the membrane of camel red blood cells, implicating that camel may be susceptible to NDV infection. In this article, we report the first isolation of NDV from the aborted fetus of a dromedary in the United Arab Emirates during the process of Middle East Respiratory Syndrome coronavirus (MERS-CoV) screening, and results of its comparative genome and phylogenetic analysis.
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.
Neither TGEV nor PEDV was detected in any of the rectal swabs collected from 160 diarrheic pigs.
Results of the PAstV detection in investigated pigs are presented on Fig. 1.
PAstV RNA was detected in all 17 investigated farms with an overall prevalence 93.2% (383/411).
Among healthy pigs 94.4% (237/251) were found to be infected by PAstV. The most affected group across age categories was the fattening pigs where nearly all animals were virus positive (98.9%; 89/90) followed by weaned pigs (94.6%; 70/74), and suckling piglets (89.7%; 78/87).
In diarrheic animals, 91.3% (146/160) pigs were infected by PAstV. The most affected group across age categories were weaned pigs (97.3%; 71/73), followed by suckling piglets (89.3%; 50/56) and fattening pigs (80.6%; 25/31).
Statistical analysis of individual age categories revealed high significant differences of astrovirus infection between diarrheic fattening (80.6%) pigs and healthy fattening (98.6%) pigs (p < 0.01, χ2 = 14.08) with even higher prevalence in healthy animals. No significant differences were observed between healthy and diarrheic in the other two age categories.
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.
Astroviruses were first discovered in stool samples of infants suffering from diarrhea in 1975. Since then, our knowledge about the molecular and phenotypic characteristics of these viruses, on the viral pathogenesis and on the spectrum of susceptible hosts has been considerably expanded. Astroviruses belong to the Astroviridae family which is, according to the International Committee on Taxonomy of Viruses (ICTV), divided into two genera: Mamastrovirus, including 19 species, designated Mamastrovirus 1–19; and Avastrovirus including three species, formerly assigned as turkey, chicken and duck astrovirus. This virus family comprises a diverse group of small, non-enveloped single-stranded RNA viruses of positive polarity with a characteristic star-like appearance. The genome consists of 6.17 to 7.72 kb with a 5′untranslated region (UTR) that is followed by three open reading frames (ORFs), a 3′UTR and eventually a poly-A tail. ORF1a and ORF1b encode non-structural polyproteins 1a and 1b that include a protease and the conserved RNA-dependent RNA polymerase (RdRp) whereas ORF 2 encodes a more divergent structural capsid protein. Altogether 19 species of mamastroviruses, have been identified with a wide geographic distribution in a great number of domestic animals, in wildlife including bats, as well as in humans. Most of the infections caused by astroviruses are assumed to be asymptomatic but, depending on the affected species, the age and immunological status of the affected host, an infection can also be associated with diarrhea, hepatitis, nephritis or, more recently, even encephalitis. In bats, astroviruses were mostly found in apparently healthy animals. Since 2008, a growing number of bat species have been found to carry astroviruses with a noticeable prevalence and diversity.
Bats are frequently considered the reservoir host for a broad variety of newly emerging viruses, especially in the tropics, although their general role in the epidemiology and spillover of zoonotic viral diseases is still not fully understood. Some of these newly emerged viruses such as corona-, henipa- and filoviruses are zoonotic and show high pathogenic potential in humans. As generally assumed for the reservoir hosts, bats do not develop severe clinical symptoms upon these viral infections. The reasons are still not fully understood and little is known about the immune system of bats and its interaction with pathogens. As the only flying mammals, bats have evolved special anatomical and physiological characteristics. Several of them appear to be relevant for their role as reservoir hosts of viral agents. As opposed to the reduced body temperature when resting, the body temperature of bats may increase during flight to above 40 °C, which is thought to mimic a fever. On the other hand, the reduced body temperature and low metabolic rate during hibernation or torpor have been discussed to negatively affect the efficient immune response to infections. This may impair viral clearance, and therefore, by transmission to juvenile bats born after hibernation, may even cause virus persistence in the affected colony. The roosting of certain bat species in gatherings of thousands if not millions of individuals is thought to facilitate high intra- and interspecies contact rates that might allow efficient virus transmission. Deforestation, growing urbanization and environmental changes have not only destroyed great parts of the bats’ habitats, but have also increased their interactions with humans and livestock. To analyze the potential health risk for humans, it has become important to study the ecology and the zoonotic potential of viruses found in bats. This review gives an overview on what is known about astroviruses in bats and their potential to cross species barriers to humans and/or livestock.
Astroviruses (AstV) are small, nonenveloped, RNA viruses that are a major cause of gastroenteritis in infants, immunocompromised people, and the elderly, and they also cause disease in mammals and birds. Despite the disease burden, little is known about the immune response to astrovirus infection. Human clinical studies have demonstrated that an antibody-mediated response may be responsible for limiting astrovirus infection and clinical disease. Recent work using small animal models and cell culture systems have revealed an important role in the innate immune response in restricting astrovirus replication and pathogenesis. This review will summarize the current knowledge of the innate and adaptive immune responses to astrovirus infection using studies of humans, small animal models, and cell culture systems and will discuss how astroviruses evade the immune system. This review will also highlight the increasing reports of astroviruses as possible causes of central nervous system disease, especially in immunocompromised individuals. Finally, we will conclude with unanswered questions, future studies, and how the use of a newly developed mouse model can enhance our understanding of the immune response to astrovirus infection, and how these responses play a role in astrovirus-induced disease.
In 2015, a gout disease emerged in 1-week-old goslings in Anhui province, which has spread to most provinces of China by 2017. The outbreak of the gosling gout disease has caused significant economic loss in goose industry. The clinical signs of the disease were characterized by white feces, leg joint enlargement with urate deposits and paralysis. At necropsy, kidney enlargement and intensive urate deposits were found in the gallbladder, knees, and ureters, and on the surfaces of cardiac, heart, liver, air sacs, trachea, and proventriculus (Fig. 1a–f). The disease lasted for 7–10 days with high morbidity and mortality. The survival goslings grew slowly and were susceptible to bacterial infection.
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.
Human enteric viruses constitute a serious public health concern, since they are capable of causing a variety of acute illnesses, including the most commonly reported acute gastrointestinal illness. They are mainly transmitted via the fecal-oral route either by person-to-person contact or by ingestion of contaminated water and food, particularly shellfish, soft fruits and vegetables. Enteric viruses are shed in enormous quantities in feces (109 to 1010/g) and have an infectious dose on the order of tens to hundreds of virions. Enteric viruses are host-specific and are not capable of replicating in the environment, but they survive for long periods of time on food or food contact surfaces or in water (ground, surface, and drinking water). These characteristics enable enteric viruses to play a significant role in food- and waterborne outbreaks. Aside from noroviruses, which have been recognized as the largest cause of outbreaks, the viruses most often implicated in outbreaks include hepatitis viruses (hepatitis A virus and hepatitis E virus), rotavirus, adenovirus (40, 41), astrovirus, enterovirus [2, 3, 4, 5, 6, 7]. Additional viruses of lesser epidemiologic importance include human bocavirus, cosavirus, parvovirus, sapovirus, tick-borne encephalitis virus (TBEV), Aichi virus, and coronavirus [8, 9, 10, 11].
Tools for rapid detection of viral pathogens are important for analyzing clinical, environmental and food samples. Detection of these enteric viruses based on their infectivity is complicated by the absence of a reliable cell culture method and the low levels of contamination of food and environmental samples. To date, real time RT-PCR has been one of the most promising detection methods due to its sensitivity, specificity, and speed. Recently, the ISO/TS 15216–1 and 15216–2 standards covering real time RT-PCR for both quantitative determination and qualitative detection of NoV and HAV in foodstuffs were published [14, 15, 16].
The aim of this study was to develop real time RT-PCR assays for detection of a total of 19 human enteric viruses (including 3 genogroupes of norovirus and 4 coronaviruses) and two control process viruses (mengovirus and murine norovirus) generally used for monitoring the recovery of viral foodstuff extraction methods. Limits of detection of the viral genomes were determined with the conventional RT-qPCR system and with the Fluidigm’s BioMark System by using the qualitative nanofluidic real-time RT-PCR array and the quantitative digital RT-PCR array. The advantages of these new detection techniques were determined by detecting and quantifying pathogenic viruses in clinical samples.
Astroviruses are currently classified into two genera, Mamastroviruses (MAstVs) and Avastroviruses (AAstVs)1. MAstVs mainly infect mammals including human, ovine, bovine, porcine, feline, canine, mink, bat, deer, mouse, sea lion, dolphin etc., whereas AAstVs generally infect aviansuch as turkey, chicken, duck, pigeon, and goose1,2. Notably, genetic variation and cross-species transmission of astrovirusespose the risk for zoonotic infection2,3. Infection with astroviruses mainly cause enteric diseases such as gastroenteritis and diarrhea in human and animals as reported initially, then nephritis in chicken and pigeon, hepatitis in ducklings, and encephalitis in human, cattle, and sheep recently, which broadens the disease pattern of astroviruses and highlights its significance2,4–6. In 2015, a gout disease emerged in 1-week-old goslings in Anhui province, which had spread to most provinces of China by 2017 with high morbidity (80–90%) and mortality (20–70%), and no pathogenic bacteria could be isolated from the diseased goslings. However, little is known about the pathogen for the goose gout disease endemic in goose flocks in China. During 2011–2012, the outbreaks of gout disease were reported in broilers in India. Through virus isolation and infection study, Bulbule et al. demonstrated that a novel chicken astrovirus (CAstV) could be as one of the causative agents for the gout disease in chicken flocks in India7. To control the spread of the goose gout disease, we investigated the pathogenic agent of the disease. Through in vitro and in vivo experiments, we identified and isolated a novel goose astrovirus different from the CAstVas a causative agent of the gout disease recently circulating in gosling flocks in China.
General practitioners enrolled 175 adult patients consulting for AD and 101 non diarrheal individuals, but we received stools samples from 138 cases and 93 controls. The two populations (cases and controls) presented similar demographic characteristics: median age of cases was 37 years [28 - 54] versus 39 years [29 - 54] for controls (p = 0.62); the proportion of women in the cases group was 45.9% versus 47.3% in the control group (p = 0.85).
Sequencing of the amplified products revealed a high homology with TAstV-2 North Carolina Q/34/1990 strain for polymerase gene and to TCoV for the 3‘UTR of turkey\UK\412\00 strain (FJ178641 and , respectively).