Dataset: 11.1K articles from the COVID-19 Open Research Dataset (PMC Open Access subset)
All articles are made available under a Creative Commons or similar license. Specific licensing information for individual articles can be found in the PMC source and CORD-19 metadata.
More datasets: Wikipedia | CORD-19
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
An infectious etiology for cancer was first documented in animals during the early part of the nineteenth century with the diagnosis of pulmonary adenocarcinoma in sheep (later attributable to jaagsiekte sheep retrovirus) (5). Animals are the host species for many oncogenes. Among the most studied are rodent (Abl, Int1/Wnt1, Int2, Notch1, Pim1/2, Runx, Tpl2), fowl (Erb-b, Fos, Myc, Src), feline (Myc), and fish (cyc) (6). For example, reticuloendothesliosis virus readily induces cancer in chickens (avian leucosis/sarcoma). The virus has been found in eggs intended for human consumption and vaccines prepared in eggs (7). A wide variety of viruses, mirroring their human analogs, are ubiquitous among animals in nature and their habitat (e.g., fecal coliform contamination) (8–10). Common types include viruses in the polyoma, adeno, retro, and papilloma family.
Animal viruses potentially express oncoproteins in human cells even though stringent replicate restrictions exist in the latter (11). The “hit and run” hypothesis posits that certain viruses interfere with the hosts immune system to cause cancer, yet do not integrate into the victims DNA (leaving no detectable fingerprints) (12). Newborn hamsters infected with polyoma virus have been shown to develop cancers, even though the cells of this species do not support virus replication (13). Similarly, tumors induced in immunocompetent mammals with Rous sarcoma virus do not present neutralizing antibodies (14). In contrast, some animal viruses [e.g., feline leukemia virus (FeLV)] have been observed to replicate in vitro in human cells (15, 16). Sera collected from 69% of 107 persons among 46 households with at least 1 FeLV gs-a positive cat tested positive for antibodies against FeLV (15). Although it is unclear exactly how antibodies directed toward animal viruses could have oncogenic or mitogenic effects on host cells, these findings support the idea that long-lasting “biological memory” of animal virus exposure can exist within the host in the absence of direct effects on host DNA.
Animal bacteria also have been implicated in cancer. The occurrence of gliomas in the brain of fowl have been noted in several reports (17–19) and these tumors have been described as having the pathognemonic encephalitic features of a pleomorphic parasite infection (e.g., hypertrophy and hyperplasia of blood-vessels; perivascular infiltration by lymphocytes, plasma cells, and monocytes; and the presence of A-D bodies) (20). Chickens spontaneously and experimentally infected with toxoplasma have been observed to develop glioma-like tumors (21, 22). A study of 16 human brain tumors observed bodies indistinguishable from the C and D phases of the fowl parasite (23). Epizootic outbreaks of toxoplasmosis have been reported in various avian species and mammals (22, 24, 25). Furthermore, toxoplasma antibodies have been isolated in the blood of exposed sheep farmers, flock animals, herder dogs, mice, and rats (26). Potential cellular mechanisms by which animal viruses and bacteria lead to tumorgenesis are shown in Figure 1.
Influenza A, B and C viruses are members of the Orthomyxoviridae family that can cause influenza in humans. Influenza A viruses exist in humans, various other mammal species, and birds; migratory or domestic waterfowl are their largest reservoir. Humans are thought to be the primary hosts and reservoir of influenza B and C viruses, although both have been identified in other hosts after reverse zoonotic transmission from humans. While influenza B virus is a common seasonal human pathogen similar to influenza A virus in its clinical presentation, influenza C virus causes primarily upper respiratory tract infections in children. Clinical manifestations (cough, fever, and malaise) are typically mild, but infants are susceptible to serious lower respiratory tract infections. Influenza C viruses co-circulate with influenza A and B viruses and causes local epidemics,. Six genetic and antigenic lineages of influenza C viruses have been described, and as in influenza B viruses, are considered monsubtypic,. Co-circulation of multiple subtypes of influenza allows for rapid viral evolution through the process of antigenic shift, a property previously only shown for influenza A viruses. Thus, both influenza B and C viruses do not have pandemic potential. In contrast, the Influenza A genus includes 17 hemagglutinin and 9 neuraminidase subtypes, and reassortment among different subtypes has repeatedly generated pandemic viruses to which the human population is naïve–. It is the animal reservoirs of diverse influenza A viruses that give them the unique property within orthomyxoviruses of causing human pandemics.
Aside from humans, influenza C virus has been isolated only from swine in China (in 1981). Genetic analysis showed a close relation between Japanese human and Chinese swine influenza C isolates,. Serological surveys in Japan and the United Kingdom found 9.9% and 19% of swine, respectively, to have positive HI antibody titers to human influenza C viruses, suggesting that the virus is not uncommon in swine,. Swine inoculated with influenza C virus had mild respiratory disease and transmitted the virus to naive swine by direct contact. Here we characterize an orthomyxovirus isolated from a clinically ill pig and show that the virus is distantly related to human influenza C virus and readily infects and is transmissible in both ferrets and pigs. Genetic and antigenic analysis suggest that this virus represents a new subtype of influenza C virus, raising the possibility of reassortment and antigenic shift as mechanisms for influenza C virus evolution which could pose a potential threat to human health.
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.
The natural reservoir of influenza A virus (infAv) is considered to be aquatic birds because all known subtypes (H1-H16 and N1-N9) of infAv have been isolated from waterfowl. InfAv can, however, infect many other mammalian species, including humans, swine, horses, ferrets, and sea mammals. There are several specific swine influenza A virus (SIV) subtypes (H1N1, H1N2 and H3N2) circulating in the pig populations in Europe, including Denmark. The Danish SIV subtype H1N2 differs from the European SIV H1N2 subtypes, in that it is a re-assortment between two circulating Danish SIV strains of the subtypes H1N1 and H3N2. The first known Danish H1N2 isolate occurred in 2003 and is therefore a relatively new strain in Denmark.
It has been described that pigs have receptors for both human and avian strains of influenza A viruses in the upper respiratory tract and therefore are susceptible to infections by both. Based on this finding, it has been proposed that pigs can act as a mixing vessel when infected by both a human and avian influenza A virus (AIV) strain to make a new reassorted virus with zoonotic and even pandemic potential. In recent years, however, there have been examples of infAv crossing the species barrier without the involvement of pigs. Infections with infAv are initiated by interactions between virus haemagglutinin and sialic acid (SA) molecules on target cells. AIV strains prefer SA-α-2,3-terminal saccharides whereas human and swine influenza virus strains prefer SA-α-2,6-terminal saccharides as receptors. A few studies have shown that the epithelial cells of the upper respiratory tract of pigs express both receptors. However, recent studies have shown a more variable distribution of the specific receptors in the deeper lung areas whereas in the trachea the SA-α-2,6-terminal saccharides are abundant. It has been described that after infections with AIV in pigs and humans the virus has shifted receptor specificity from SA-α-2,3 to SA-α-2,6 as a part of the adaptation to the new host by the virus. This shift in receptor specificity has been linked to specific amino acid substitutions in the HA molecule, but the exact determinants of the host specificity of infAv have not been fully elucidated.
Specific lectins have been the chosen method for detecting SA receptors. The Sambucus Nigra (SNA) lectin is specific for SA-α-2,6 bindings and the Maackia Amurensis (MAA) lectin is specific for SA-α-2,3 bindings of the SA molecules. In order to detect SA-α-2,3-terminal saccharides it is necessary to use two isoforms of MAA lectin: MAAI and II because the two isoforms are different in the way they recognise the inner sugar structures of SA-α-2,3. A more thorough investigation of the receptor distribution in the respiratory tract of pigs would give a more nuanced picture of the infection dynamic of different infAv in pigs. This, together with investigation of the predilection site of different infAv in the respiratory tract tissue, would enable us to improve our understanding of the mechanisms of infection regarding pathogenesis and host range determination.
The aim of the study was to investigate the tissue and cell predilection sites of avian and swine influenza A viruses, respectively, and SA-α-2,3/2,6-terminal saccharide receptor distribution in the respiratory tract of pigs by the use of immunohistochemical methods and lectin staining.
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).
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.
Canine enteritis can be caused by a number of viral, bacterial or parasitic agents. The most common viral entero-pathogens are canine parvovirus (CPV) and coronavirus (CCoV),, although other agents, such as canine adenovirus (CAdV) type 1, canine distemper virus (CDV), rotaviruses, reoviruses, and caliciviruses, have been associated with enteric disease in dogs. In recent years, novel viruses have been discovered from dogs with enteritis, namely noroviruses, sapoviruses, astroviruses, and kobuviruses,.
More recently, a dog circovirus (DogCV) was detected in dogs with vasculitis and/or hemorrhagic diarrhoea in the US (13). Circoviruses (family Circoviridae, genus Circovirus) are non-enveloped, spherical viruses with a small monomeric single-strand circular DNA genome of about 2 kb in length. According to the most recent release of the Universal Virus Database of the International Committee on Taxonomy of Viruses, the genus Circovirus consists of eleven recognized species, including Porcine circovirus 1 (PCV-1), Porcine circovirus 2 (PCV-2), Canary circovirus (CaCV), Beak and feather disease virus (BFDV), and other viruses of domestic and wild birds (http://ictvdb.bio-mirror.cn/Ictv/fs_circo.htm). Porcine and avian circovirus infections are characterized by clinical courses that may vary from asymptomatic infections to lethal disease.
Two independent studies have shown that, similar to other animal circoviruses, DogCV possesses an ambisense genomic organization with 2 major inversely arranged ORFs encoding for the replicase and capsid proteins, respectively,. The canine virus, firstly detected in serum samples, was later recognized as causative agent of necrotizing vasculitis and granulomatous lymphadenitis.
The aim of this paper is to report the detection and molecular characterisation of DogCV in dogs with acute gastroenteritis in Italy. The full-length genome of the Italian prototype strain was determined and analyzed in comparison with American strains and other circoviruses.
Pet dogs play an important role in humans’ daily lives. Recently, the emergence of new pathogens and the continuous circulation of common etiological agents in dog populations have complicated canine diseases. Among these diseases, canine infectious respiratory diseases (CIRD) and viral enteritis pose notable threats to dog health.
CIRD are complex and include canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine influenza virus (CIV), canine parainfluenza virus (CPIV), canine herpesvirus (CHV), canine reovirus, Bordetella bronchiseptica and other pathogenic agents [2–4]. Among these, CAV-2, CDV or CPIV have frequently been detected in dogs with CIRD, according to previous studies [5, 6]. Avian-origin H3N2 CIV has been detected in domestic dogs in South Korea and China since 2007 [7, 8]. H3N2 CIV is now circulating in dog populations in China, South Korea, Thailand, and even the United States [9–11]. Distinguishing these pathogens can be challenging, because dogs often show similar clinical signs of infection with these viruses, such as low-grade fever, nasal discharge and cough. These respiratory symptoms are flu-like and difficult to diagnose.
Canine viral enteritis is common in dogs with acute vomiting and diarrhea. Canine parvovirus (CPV) is one of the major viruses leading to acute gastroenteritis in dogs; CPV infection is characterized by fever, severe diarrhea and vomiting, with high morbidity. Puppies tend to be intolerant of CPV infection and have higher mortality than adult dogs because of myocarditis and dehydration [14, 15]. Canine coronavirus (CCoV) is characterized by high morbidity and low mortality. Dogs infected with CCoV alone are likely to have mild diarrhea, whereas the disease may be fatal when coinfection by CCoV and CPV, CDV or canine adenovirus type 1 (CAV-1) occurs [16, 17]. CAV-2 is associated with mild respiratory infection and episodic enteritis [18, 19]. Canine circovirus (CanineCV), a newly discovered mammalian circovirus, was first reported by Kapoor et al. in 2012. CanineCV has been detected in dogs with severe hemorrhagic diarrhea, and it is more common in puppies than in adults [21, 22]. Coinfection of CanineCV with other intestinal pathogens (CPV or CCoV) is closely related to the occurrence of intestinal diseases [23, 24]. Dogs with intestinal diseases are often infected with one or more viruses, and their clinical symptoms are similar [17, 25, 26], making clinical differential diagnosis difficult. To date, no multiplex PCR (mPCR) method has been developed to detect CanineCV and other enteropathogens.
An effective diagnostic tool is important for the prevention, control and treatment of CIRD and viral-enteritis-related viral diseases. Although many methods exist to detect CIRD and canine viral enteritis, most can detect only 2 or 3 pathogens, and the current lack of systematic and comprehensive detection methods makes diagnosis impractical and time consuming [4, 27, 28]. Because mPCR can simultaneously detect multiple pathogens in a timely and inexpensive manner, this technique has become increasingly popular. Therefore, in this study, two new mPCR methods were developed for the detection of canine respiratory viruses (CRV, including CAV-2, CDV, CIV and CPIV) and canine enteric viruses (CEV, including CAV-2, CanineCV, CCoV and CPV), and we indicated that the mPCR methods established here are simple and effective tools for detecting the viruses of interest.
More than 70% of the emerging infectious disease agents are caused by microbes jumping from animals into human. This has been well exemplified by the highly fatal human infection due to avian influenza A H5N1 in 1997. The outbreak of severe acute respiratory syndrome (SARS) caused by a novel coronavirus in 2003, confirmed again that microbes can jump species from animals to humans with unpredictable consequence. The human SARS coronavirus was traced to caged civets in the market, and later Chinese horseshoe bat, Rhinolophus sinicus, was suggested to be a likely reservoir of SARS coronavirus. Bats are ideal incubators for new emerging infectious agents as they are mammals which roosted together and can fly over vast geographical distance. This has reignited the interest in seeking for new bat viruses including many bat coronaviruses and the recent discovery of bat influenza virus. Besides the SARS coronavirus, viruses in bats often infect human through intermediate hosts such as horses for Hendra virus, pigs for Nipah virus, and chimpanzees for Ebola virus. It is therefore important to catalogue as comprehensively as possible the animal viruses present in wild life especially the bats and birds, the food animals such as pigs and cattles, the pet animals such as cats and dogs, and monkeys which are phylogenetically close to humans. Using consensus primer polymerase chain reaction (PCR) screening, we have been able to discover relatively closely related species of virus in many different animals,–. However more distant or novel families of virus can only be found by metagnenomics using deep sequencing with the newer generation sequencers,. We report in this paper the discovery and characterization of a novel bat papillomavirus (PV) from rectal swab samples randomly collected from asymptomatic wild, food and pet animals using a metagenomic approach.
Porcine circoviruses are small non-enveloped viruses with single-stranded circular DNA and belong to the genus Circovirus and the family Circoviridae. Two types of PCVs (PCV1 and PCV2) have been reported in pigs. PCV1 is non-pathogenic to pigs, while PCV2 is related to porcine circovirus-associated diseases (PCVAD). In 2016, a novel circovirus PCV3 was first detected in pigs in the US shown as porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure, multi-systemic inflammation and cardiac pathology [6, 7]. The PCV3 genome is 2000 nucleotides in length with two major inversely arranged ORFs encoding replicase (Rep) and capsid (Cap) proteins [6, 7]. So far, the novel pathogen has been reported in major pig-producing countries including China, Poland, South Korea, Italy, Brazil, Germany, Thailand, Denmark, Spain, Sweden and Russia [8–17]. PCV3 was also identified in pigs with no clinical signs of infection or disease conditions [9–18] only [9, 18] after this sentence. Please delete ref numbers 10 to 17. Here we report the prevalence of PCV3 in pig herds in Zhejiang, a southeastern province of China, by molecular method and indirect ELISA and its co-infections with other major swine viral pathogens.
Circoviruses are non-enveloped DNA viruses belonging to the genus Circovirus of the family Circoviridae, and contain a small circular, single stranded ~2 kb DNA genome1. This genus harbors viruses that infect domestic and wildlife animal species, including porcine circoviruses (PCV-1 and -2), canary circovirus (CaCV) and beak and feather disease virus (BFDV) of birds2–5. Next generation sequencing (NGS) has recently allowed the discovery of additional mammalian circoviruses including PCV-3 in pigs6 and canine circovirus-1 (CanineCV-1) in dogs1. Infection with CanineCV-1, recently re-classified as ‘CanineCV’7, has been associated with several disease entities accompanied by manifestations like vasculitis, hemorrhages, thrombocytopenia, neutropenia and diarrhea2,7–9, although it is also detected in healthy dogs1,8,10. Interestingly, dogs infected with CanineCV are often co-infected with other enteric or respiratory pathogens2,7,10,11. Therefore, the pathogenic role of CanineCV is not clear. To date, CanineCV-infected dogs have been documented in several countries including the USA1,8,11, Italy9, Germany7, China (GenBank accession number: KT946839) and Taiwan2.
Besides genetic mutation, recombination is a driver of circovirus evolution, as several previous studies have shown genetic recombination within the Circoviridae family. These include BFDV12, Torque teno virus13 and PCV-214–17, and have contributed to genetic diversity of these viruses. Types of recombination mechanisms include homologous recombination in which homologous sequences are exchanged, non-homologous recombination in which genome regions are rearranged, deleted, duplicated or inserted into the host genome and reassortment in which whole genome components of the virus get exchanged between strains and species18. In homologous recombination, any interruption during replication, such as the encounter of strand break sites or clashes between replication and transcription complexes, can create temporary detachment of the replication enzyme. The enzyme can then use another similar template to reinitiate replication, thus generating a recombinant genome18. Thus far, genetic recombination of CanineCV genomes has not been documented. In the present study, we have molecularly characterized CanineCV strains from Thai dogs by next generation sequencing with special emphasis on the occurrence of genetic recombination.
The porcine circovirus (PCV) belongs to the family Circoviridae and contains a single-stranded circular DNA genome. There are three types of PCV: porcine circovirus type 1 (PCV1), porcine circovirus type 2 (PCV2) and porcine circovirus 3 (PCV3). During the past few decades, PCV2 has been widely studied and is considered to be the main pathogen responsible for porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are characterized as clinical or subclinical PCV2 infections among pigs. The most representative symptoms of the diseases include porcine dermatitis and nephropathy syndrome (PDNS), which mainly occurs during the growing or finishing stage of pigs; postweaning multisystemic wasting syndrome (PMWS), which affects nursery and growing pigs; and porcine respiratory disease complex (PRDC), which usually occurs in pigs 14–20 weeks of age.
To date, the exact mechanisms of PCVD/PCVAD are currently unknown. However, many studies have reported co-infection with other swine pathogens, such as porcine reproductive and respiratory syndrome virus, porcine parvovirus, swine influenza virus, Mycoplasma hyopneumoniae, and Salmonella spp., are important cofactors that may enhance PCV2 infection and the severity of PCVD/PDVAD. Furthermore, vaccination failure, stress or crowding together with PCV2-infected animals also cause PCVD/PCVAD. As co-infections with viruses are frequently detected in domestic pigs and wild boars, we discuss co-infections of pigs with PCV2 and other swine viruses in this review. Furthermore, co-infections of different PCV2 strains, which cause recombination and genomic shifts in recent years, are also reviewed.
Porcine circoviruses (PCVs) are members of the Circovirus genus of the Circoviridae family. Currently, there are three species in the genus, PCV type 1 (PCV1), PCV type 2 (PCV2), and PCV type 3 (PCV3), respectively. In 1974, PCV1 was discovered as a contaminant in porcine kidney cell lines (1). Subsequent studies have confirmed that PCV1 is apathogenic in pigs (2). In late 1990s, a new porcine disease, called post-weaning multisystemic wasting syndrome (PMWS), emerged in North America and Europe (3–6), and PCV2 was confirmed as the causal pathogen (7, 8). PCV2 has a global distribution and diverse genotypes (9, 10). In 2016, the third PCV, named PCV3, was discovered using high-throughput sequencing technology in U.S. swine herds suffering from porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure and other syndromes (11, 12). A recent study suggested that PCV3 fulfilled Koch's postulates and could cause PDNS in piglets (13).
PCVs, especially PCV2 and PCV3, are very common in pigs, and can cause diverse clinical presentations including PMWS, PDNS, reproductive failure, interstitial pneumonia, and so on. Both, PCV2 and PCV3 have garnered immense interest in the world swine industry. Hitherto, most studies found in literature have focused on PCVs derived from swine sources. Occasionally, PCVs have also been isolated from non-porcine animals, biological products, and environmental samples.
Coronaviruses (CoVs) are enveloped, single-stranded, positive-sense RNA viruses in the family Coronaviridae that is within the order Nidovirales. The Coronaviridae contain at least four major genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Porcine CoVs are significant enteric and respiratory pathogens of swine. In 1946, porcine transmissible gastroenteritis virus (TGEV), an alphacoronavirus (α-CoV), was identified as the cause of a devastating enteric disease of pigs in the United States (1). A second U.S. porcine α-CoV, porcine respiratory coronavirus (PRCV), was officially identified in 1984 (2). PRCV is a deletion mutant of TGEV that alters viral tropism from intestinal to respiratory epithelia (3, 4). In swine, PRCV replicates almost exclusively in the respiratory tract and closely resembles other porcine viral pneumonias (2–4). In 1971, a new α-CoV, porcine epidemic diarrhea virus (PEDV), was identified in the United Kingdom (5). Both TGEV and PEDV replicate in small-intestinal enterocytes, causing life-threatening acute enteric disease in suckling piglets that is characterized by profuse watery diarrhea, emesis, and resultant dehydration (1, 6, 7). Morbidity rates are high (80 to 100%), as are mortality rates (50 to 90%) (1, 8). Since 2010, variant strains of PEDV differing in sequences from the classic European strain (CV777) have appeared in China, South Korea, Japan, and many Asian countries, causing up to 100% mortality in suckling piglets (8, 9). In May 2013, PEDV was identified as a new cause of neonatal diarrhea in Iowa (10, 11). Infection rapidly spread to more than 30 states, Canada, and Mexico and caused significant economic losses in the swine industry (12–14). Sequence analyses suggest that U.S. PEDV strains originated from China (12).
The Deltacoronavirus genus has been only recently defined by genomic sequence analysis of both pig and avian isolates (15). Since 2009, avian deltacoronaviruses have been detected in a wide range of domestic and wild birds (15–17). The porcine deltacoronaviruses (PdCV) Hong Kong (HK) strains HKU15-155 and HKU15-44 were recently detected in rectal swabs from pigs (15). The potential of the HKU15-155 and HKU15-44 PdCVs to cause significant clinical disease in swine is not known. In mid-January 2014, PdCV was identified in fatal cases of PEDV-negative diarrhea in Ohio piglets (18). Field reports document a history and clinical presentation (vomiting, diarrhea, and dehydration) typical of TGEV and PEDV; like for the other swine enteric CoVs, morbidity and mortality rates at PdCV-infected farms are high (18–21). In some instances, PdCV is the only virus recovered from these diarrhea outbreaks; in others, it may be present as a coinfection with PEDV. To date, outbreaks have been documented in more than 20 states in the United States. In April 2014, a PdCV strain (KOR/KNU14-04/2014) was also identified in feces from diarrheic piglets in South Korea (22).
Aside from genomic sequence data, nothing is known about the U.S. PdCV. Although the virus is identified in diarrhea outbreaks, experimental studies that directly demonstrate its disease-causing potential remain to be shown. The objective of this study is to characterize the U.S. PdCV isolate in terms of genetic characteristics, phylogeny, and virulence in gnotobiotic (Gn) and conventional piglets. Genomic sequencing found that U.S. PdCV strains share 99.6 to 99.7% homology with each other and 99.0 to 99.1% homology with Hong Kong isolates (HKU15-155 and HKU15-44). We found that the U.S. PdCV strains caused severe diarrhea, vomiting, and dehydration clinically indistinguishable from those caused by PEDV and TGEV. Histologically, the PdCV strains caused severe lesions in the stomach and small intestine and mild interstitial pneumonia in lungs. Collectively, our study provides the first proof that PdCV causes significant enteric disease in swine.
In April 2011, nasal swabs from 15-week old swine exhibiting influenza-like illness were submitted to Newport Laboratories, Worthington, Minnesota, for virus isolation. Real-time reverse transcription PCR (rt-RT-PCR) was negative for influenza A virus. In swine testicle (ST) cells, the viruses caused influenza-like cytopathic effects (CPE) by day 3. The cell culture harvests were again negative for influenza A virus by rt-RT-PCR. Electron microscopic (EM) studies of the cell cultures demonstrated features characteristic of an Orthomyxovirus (Fig. 1). Negative-staining EM showed enveloped spherical to pleomorphic viral particles approximately 100–120 nm in diameter (Fig. 1A). The virion surface contained dense projections 10–13 nm in length and 4–6 nm in diameter. Thin-section EM studies of infected cells revealed filamentous budding of virions from the plasma membrane (Fig. 1B). These data strongly suggested the virus to be a member of the family Orthomyxoviridae. Enzymatic assays revealed that the virus had negligible neuraminidase but detectable O-acetylesterase activity using 4-nitrophenyl acetate, suggesting it to be a member of the influenza C genus. However, further RT-PCR analysis was negative for influenza B and C viruses. RT-PCR or PCR assays to detect porcine reproductive and respiratory syndrome virus, porcine coronavirus, and porcine circovirus were also negative (data not shown).
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.
Respiratory tract infections account for great morbidity and mortality in the human population and caused almost 4 million deaths in 2008. A large proportion of these infections have viral etiology, in particular in children. While previous studies have identified a number of viral etiologic agents, such as rhinovirus, coronavirus, influenzavirus, parainfluenzavirus, respiratory syncytial virus and adenovirus, approximately 30% of all presumed viral cases fail diagnostic tests for these agents. Thus, the tests are either inefficient or the causative agent is unrelated to any of the known viruses associated with respiratory infections. In fact, since 2001, several previously undescribed viruses have been identified by analysis of the human respiratory tract, including metapneumovirus, severe acute respiratory syndrome (SARS) and human bocavirus.
Viruses have limited means of transmission between organisms, but the respiratory tract is one important route. Many viruses that are primarily associated with non-respiratory infections, for example, herpes viruses, enteroviruses and parvovirus B19,, are still transmitted through the respiratory tract. Therefore, the respiratory tract is an excellent starting point for an in-depth characterization of the human virome and to identify novel human viruses.
In recent years, viral metagenomics has become an established method both for finding novel viruses and for detecting the presence of known viruses in new environments,,,,. We have sequenced and characterized the virome, in respiratory tract secretions from hospitalized patients, mainly infants and children, with severe lower respiratory tract infections. While many pathogens of the respiratory tract is of bacterial origin, due to chemical enrichment for virus, the bacterial sequences found in this study are likely biased and not representative for these patients. Even so, we have provided a crude characterization of the bacterial content found in these samples along with contigs of other origin. We confirmed that the lower respiratory tract was a milieu that was rich in viruses, in these patients. Many known pathogens were identified, but we also found unexpected virus families as well as one novel rhinovirus C type.
PCV-3 DNA was also detected in pigs with respiratory disorders, as already indicated in the first report of this virus (21). Two more studies reported PCV-3 genome in animals from China with abdominal breathing and lesions including lung swelling and congestion (87, 99). More recently, the viral genome has been detected in fattening pigs from Thailand suffering from porcine respiratory disease complex (PRDC), characterized by coughing, dyspnea, fever and anorexia; the prevalence was higher in diseased animals (60%; 15 out of 25) than in healthy ones (28%; 7 out of 25) (91).
Multisystemic inflammation and myocarditis were initially linked with the presence of PCV-3 (22). One single study described PCV-3 in weaned pigs that suffered from gastro-intestinal disorders (diarrhea), showing higher prevalence in pigs with clinical signs (17.14%, 6 out of 35) compared to those with non-diarrhea signs (2.86%; 1 out of 35) (87). In another report, animals with congenital tremors were analyzed and PCV-3 was the only pathogen found in the brain, with high amount of viral DNA (101).
A newly described canine circovirus (CanineCV) was identified recently in serum from healthy dogs. Since then, several countries have reported the molecular detection of CanineCV in cases associated with clinical disease, ranging from sudden death of puppies with bloody diarrhea to respiratory syndromes [2–6]. Lesions found include necrotizing vasculitis, lymphoid necrosis, granulomatous inflammation and necrosis of intestinal crypts and Peyer’s patches. Some characteristics of the disease observed in dogs (enteritis, pneumonia, lymphadenitis) were also present in pigs infected with porcine circovirus 2 (PCV-2), which was found to be genetically related.
A number of case-control studies have been published, most of them describing significant association between diarrhea and CanineCV detection [8–11]. The role of this new virus in pathogenesis is however difficult to assess since it is also found in feces from healthy dogs. Furthermore, the first description was done from serum samples from six healthy animals and there have been recent reports of CanineCV in serum samples of dogs from Brazil and China [12, 13]. Additionally, coinfection with other viral pathogens, mainly canine parvovirus (CPV), but also canine distemper virus, canine coronavirus, and canine influenza virus is present in CanineCV positive dogs with clinical symptoms at rates between 50 to 100% [4, 6, 8–11]. Viral coinfection is also a main feature of PCV-2 infection [14, 15].
Circoviruses belong to the family Circoviridae, genus circovirus; they are small, non-enveloped virus with a circular single strand DNA genome of around 2000 bp. The genome contains two main (and opposite) transcription units which encode two ORFs, a replicase associated protein (Rep) and the capsid protein (Cap). CanineCV sequences submitted to Genbank are quite similar differing slightly from those identified in wildlife. Nevertheless, the division of CanineCV into two genotypes (CanineCV-1 and Canine CV-2) based on the cap gene sequence has been proposed very recently.
In this work, we present, to our knowledge, the first report of a complete full-length CanineCV genome sequence from South America.
Coronaviruses (CoVs) are enveloped, single-stranded, positive-sense RNA viruses that can infect and cause diseases in avian and mammal species, including humans. CoVs contain the largest known RNA genomes and can be genetically divided into four genera; namely, Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Deltacoronavirus (DCoV) genus was mainly discovered in a variety of avian species and pigs. Porcine DCoV (PDCoV) was first detected in pigs during a molecular surveillance of CoVs in mammals and birds in Hong Kong in 2012, while the first PDCoV outbreak in swine herds was reported in 2014 in the United States. Thereafter, PDCoV was rapidly identified in many countries, including China, Canada, South Korea, Lao People’s Democratic Republic, Thailand, and Vietnam. PDCoV can cause severe diarrhoea, vomiting, and dehydration in suckling and nursing piglets, and the clinical symptoms are indistinguishable from those caused by porcine epidemic diarrhoea virus (PEDV) and transmissible gastroenteritis virus (TGEV). PDCoV has caused serious economic losses for the pig industries. However, there are no effective reagents and vaccines to control PDCoV.
The host range of CoVs is expanding from wildlife to humans; generally, mammals are thought to be the host for Alphacoronavirus and Betacoronavirus, while avian is considered to be the host for Gammacoronavirus and DCoV. Some CoVs can be transmitted to different animal species, and subsequently adapt to the new host, even to humans. Examples include the severe acute respiratory syndrome CoV (SARS-CoV) and middle east respiratory syndrome CoV (MERS-CoV), which were transmitted by civet cats and camels, respectively, to humans, and caused great harm to humans. The novel swine acute diarrhoea syndrome coronavirus (SADS-CoV) was also verified to be a bat-related CoV that was 98.48% identical in genome sequence to the bat HKU2-CoV, which originated from the same genus of horseshoe bats as SARS-CoV. However, little was known about the natural reservoir of these CoVs. DCoVs have been mainly found in wild birds in early research, but recent findings suggested that DCoVs are also present in mammals. With the detection of PDCoV in pig herds, it was confirmed that PDCoV had a close relation to birds’ DCoV, especially with sparrow CoV HKU17, which suggested there might exist bird-to-mammal transmission of PDCoV. Meanwhile, DCoVs were detected previously in some small wild mammals, such as Asian leopard cats and Chinese ferret badgers. The S genes of the DCoVs isolated from these mammals were closely related to those of PDCoV identified in pigs, with the nucleotide similarity over 99.8%. On the basis of these findings, we deduce that the potential interspecies transmission of PDCoV may exist between these wild small mammals and pigs, as well as between domestic pigs and birds/avian.
To date, the origin of the novel PDCoV is still unknown. It was reported that PDCoV can infect 3- to 7-day-old gnotobiotic (Gn) calves with a high level of viral RNA titer in feces and specific IgG antibody in sera, but did not show any clinical symptoms and histological lesions. Recently reports showed that PDCoV could infect human and chicken cells in vitro, indicating that PDCoV has the potential to infect chickens and humans to some extent. Given the broad host ranges of PDCoV, we speculate that PDCoV may infect other mammalian and avian species.
Whether the PDCoV really has the ability to infect chickens in vivo, and the exact mechanisms of the interspecies transmission and the pathogenicity of this novel virus, is largely unknown. Thus, in our study, the chicken embryos and specific pathogen free (SPF) chickens were used to evaluate the PDCoV infection. Our data indicated that PDCoV can infect three lines of chicken embryos, including White-feather Broiler, Hyline Layer, and SPF chicken embryos, and PDCoV can be passaged on these chicken embryos. Furthermore, we investigated the susceptibility of chickens to PDCoV infection. The PDCoV-inoculated chickens showed mild diarrhea symptoms; positive PDCoV RNA in feces and multiple organs; and mild histology lesions in the lung, kidney, and intestinal tissues. Our data suggested that chickens are susceptible to PDCoV infection, indicating that PDCoV may have the potential for cross-species transmission between pigs and chickens.
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).
Pigeon circovirus (PiCV) is classified in the genus Circovirus of the Circoviridae family. It is a small non-enveloped single-stranded circular DNA virus with approximately 2030 base pairs (bp) ambisense genome. The genome of PiCV contains at least two major open reading frames (ORFs). Located on the virion sense strand ORF, V1, encodes the replicase protein (Rep protein) which is involved in rolling circle PiCV DNA replication. Located on the complementary sense strand ORF, C1, encodes the viral capsid protein (Cap protein, CP) [1, 2]. The CP of circoviruses has been documented to exhibit antigenic properties, as confirmed in the case of porcine circovirus genotype 2 (PCV2), psittacine circovirus, and pigeon circovirus [3–5].
Like other circoviruses, PiCV is an immunosuppressive factor. Infection with this virus leads to the atrophy of the immune system organs and to lymphocyte apoptosis [6–8]. Pigeons immunosuppressed by PiCV infection are predisposed to concomitant infections with other viruses (pigeon herpesvirus) or bacteria, like Escherichia (E.) coli and Chlamydia (C.) psittaci [9–11]. The combination of various immunosuppressive factors (PiCV infection and stress associated with trainings and racing of young pigeons) with accompanying infections leads to a clinical complex disease called young pigeon disease syndrome (YPDS) [9, 12, 13]. The type and intensity of clinical symptoms of YPDS are correlated with the type of the confounding factor. Initial symptoms are relatively non-specific, but after 2–3 days increased thirst and regurgitation from the crop is usually noticed. Crops are often filled with large volumes of water combined with mucus and refluxed duodenal contents. Other symptoms include diarrhea, apathy, feather ruffling or reluctance to training. Those birds are disqualified from racing. For the reason of a very high global prevalence of PiCV infections approximating 70%, the YPDS is currently the biggest health issue in pigeon breeding [10, 12, 14, 15]. The global spreading of PiCV infections in pigeon population is probably due to pigeon racing and intercontinental trade.
The asymptomatic infections with this virus are quite common and approximate 40% [10, 16–19]. Their high prevalence in reproductive pigeons poses problems with disease control. The laboratory diagnosis is limited only to screening for PiCV genetic material with molecular methods. The possibility of detecting anti-PiCV antibodies in subclinically infected pigeons has been described as well. Because the laboratory culture of PiCV has so far proved unsuccessful, a scientific project was designed to develop an alternative method for obtaining an antigen which is recombinant capsid protein of pigeon circovirus (PiCV rCP). This protein could be used as an antigen in a sub-unit vaccine against this virus. A previous study has revealed PiCV rCP to be immunogenic to pigeons and to stimulate both cell-mediated and humoral immunity. Due to high prevalence of PiCV asymptomatic infections [18, 19], it is very likely that the subclinically infected pigeons will be vaccinated in practice. Bearing in mind the potential immunosuppressive effect of PiCV, it is important to compare the immune response to PiCV rCP in pigeons asymptomatically infected with PiCV (natural infection) to that in the uninfected pigeons, before the protectivity of the vaccine is tested. The aim of this study was, therefore, to answer a question if subclinically infected with PiCV pigeons would develop a similar immune response to PiCV rCP to that developed by the uninfected birds.
Pharyngeal and anal swabs were collected from 3,055 individual small mammals captured from July 2013 to July 2016 in 20 provinces across China (Fig. 1a and Additional file 1: Table S1). These comprised 50 rodent species of the families Muridae, Cricetidae, Sciuridae, Dipodidae, Chinchillidae, and Gliridae; two lagomorphs of the family Ochotonidae; and three soricomorphs of the family Soricidae that reside in urban, rural, and wild areas throughout China. The most common species sampled were Apodemus agrarius, Niviventer confucianus, Rattus norvegicus, Rattus tanezumi, Rattus losea, and Sorex araneus. Due to repeated sampling of some species in the same location, swabs were combined into 110 pools for analysis.