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Farmed mammals may act as hosts for zoonotic viruses that can cause disease outbreaks in humans. This SnapShot shows which farmed mammals, and to what extent, are of particular risk of harboring and spreading viruses from viral families that are commonly associated with zoonotic disease. It also discusses genome surveillance methods and biosafety measures. To view this SnapShot, open or download the PDF.
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Virus , Zoonosis , Animales , Humanos , Mamíferos , Brotes de Enfermedades , Medición de RiesgoRESUMEN
Bats, rodents, and shrews are the most important animal sources of human infectious diseases. However, the evolution and transmission of viruses among them remain largely unexplored. Through the meta-transcriptomic sequencing of internal organ and fecal samples from 2,443 wild bats, rodents, and shrews sampled from four Chinese habitats, we identified 669 viruses, including 534 novel viruses, thereby greatly expanding the mammalian virome. Our analysis revealed high levels of phylogenetic diversity, identified cross-species virus transmission events, elucidated virus origins, and identified cases of invertebrate viruses in mammalian hosts. Host order and sample size were the most important factors impacting virome composition and patterns of virus spillover. Shrews harbored a high richness of viruses, including many invertebrate-associated viruses with multi-organ distributions, whereas rodents carried viruses with a greater capacity for host jumping. These data highlight the remarkable diversity of mammalian viruses in local habitats and their ability to emerge in new hosts.
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Game animals are wildlife species traded and consumed as food and are potential reservoirs for SARS-CoV and SARS-CoV-2. We performed a meta-transcriptomic analysis of 1,941 game animals, representing 18 species and five mammalian orders, sampled across China. From this, we identified 102 mammalian-infecting viruses, with 65 described for the first time. Twenty-one viruses were considered as potentially high risk to humans and domestic animals. Civets (Paguma larvata) carried the highest number of potentially high-risk viruses. We inferred the transmission of bat-associated coronavirus from bats to civets, as well as cross-species jumps of coronaviruses from bats to hedgehogs, from birds to porcupines, and from dogs to raccoon dogs. Of note, we identified avian Influenza A virus H9N2 in civets and Asian badgers, with the latter displaying respiratory symptoms, as well as cases of likely human-to-wildlife virus transmission. These data highlight the importance of game animals as potential drivers of disease emergence.
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Animales Salvajes/virología , Enfermedades Transmisibles Emergentes/virología , Reservorios de Enfermedades , Mamíferos/virología , Viroma , Animales , China , Filogenia , ZoonosisRESUMEN
Despite the discovery of animal coronaviruses related to SARS-CoV-2, the evolutionary origins of this virus are elusive. We describe a meta-transcriptomic study of 411 bat samples collected from a small geographical region in Yunnan province, China, between May 2019 and November 2020. We identified 24 full-length coronavirus genomes, including four novel SARS-CoV-2-related and three SARS-CoV-related viruses. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome, although it possessed a more divergent spike gene. The other three SARS-CoV-2-related coronaviruses carried a genetically distinct spike gene that could weakly bind to the hACE2 receptor in vitro. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species, with the largest contiguous hotspots extending from South Laos and Vietnam to southern China. Our study highlights the remarkable diversity of bat coronaviruses at the local scale, including close relatives of both SARS-CoV-2 and SARS-CoV.
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COVID-19/virología , Quirópteros/virología , Coronavirus/genética , Evolución Molecular , SARS-CoV-2/genética , Secuencia de Aminoácidos , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Asia Sudoriental , China , Coronavirus/clasificación , Coronavirus/aislamiento & purificación , Fenómenos Ecológicos y Ambientales , Genoma Viral , Humanos , Modelos Moleculares , Filogenia , SARS-CoV-2/fisiología , Alineación de Secuencia , Análisis de Secuencia de ARN , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Zoonosis ViralesRESUMEN
Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a "laboratory escape" scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.
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SARS-CoV-2/fisiología , Animales , Evolución Biológica , COVID-19/virología , Humanos , Laboratorios , SARS-CoV-2/genética , Zoonosis/virologíaRESUMEN
The ongoing pandemic of a new human coronavirus, SARS-CoV-2, has generated enormous global concern. We and others in China were involved in the initial genome sequencing of the virus. Herein, we describe what genomic data reveal about the emergence SARS-CoV-2 and discuss the gaps in our understanding of its origins.
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Betacoronavirus/genética , Quirópteros/virología , Infecciones por Coronavirus/virología , Reservorios de Enfermedades/virología , Neumonía Viral/virología , Animales , Animales Salvajes , COVID-19 , China , Infecciones por Coronavirus/transmisión , ADN Ambiental , Genoma Viral , Pandemias , Neumonía Viral/transmisión , SARS-CoV-2 , Análisis de Secuencia de ARN , Zoonosis/virologíaRESUMEN
We know less about viruses than any other lifeform. Fortunately, metagenomics has led to a massive expansion in the known diversity of the virosphere. Here, we discuss how metagenomics has changed our understanding of RNA viruses and present some of the remaining challenges, including characterization of the "dark matter" of divergent viral genomes.
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Variación Genética , Genoma Viral/genética , Metagenómica/métodos , Virus/genética , Evolución Molecular , Filogenia , Virus ARN/clasificación , Virus ARN/genética , Virus/clasificaciónRESUMEN
The occurrence of a spontaneous nephropathy with intranuclear inclusions in laboratory mice has puzzled pathologists for over 4 decades, because its etiology remains elusive. The condition is more severe in immunodeficient animals, suggesting an infectious cause. Using metagenomics, we identify the causative agent as an atypical virus, termed "mouse kidney parvovirus" (MKPV), belonging to a divergent genus of Parvoviridae. MKPV was identified in animal facilities in Australia and North America, is transmitted via a fecal-oral or urinary-oral route, and is controlled by the adaptive immune system. Detailed analysis of the clinical course and histopathological features demonstrated a stepwise progression of pathology ranging from sporadic tubular inclusions to tubular degeneration and interstitial fibrosis and culminating in renal failure. In summary, we identify a widely distributed pathogen in laboratory mice and establish MKPV-induced nephropathy as a new tool for elucidating mechanisms of tubulointerstitial fibrosis that shares molecular features with chronic kidney disease in humans.
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Nefritis Intersticial/virología , Parvovirus/aislamiento & purificación , Parvovirus/patogenicidad , Animales , Australia , Progresión de la Enfermedad , Femenino , Fibrosis/patología , Fibrosis/virología , Humanos , Riñón/metabolismo , Riñón/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Nefritis Intersticial/fisiopatología , América del Norte , Infecciones por Parvoviridae/metabolismoRESUMEN
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa was the largest recorded. It began following the cross-species transmission of EBOV from an animal reservoir, most likely bats, into humans, with phylogenetic analysis revealing the co-circulation of several viral lineages. We hypothesized that this prolonged human circulation led to genomic changes that increased viral transmissibility in humans. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolate and introduced amino acid substitutions that defined viral lineages. Mutant GPs were used to generate a panel of pseudoviruses, which were used to infect different human and bat cell lines. These data revealed that specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells. Such increased infectivity may have enhanced the ability of EBOV to transmit among humans and contributed to the wide geographic distribution of some viral lineages.
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Evolución Biológica , Ebolavirus/fisiología , Fiebre Hemorrágica Ebola/virología , Especificidad del Huésped , África Occidental/epidemiología , Animales , Quirópteros/virología , Brotes de Enfermedades , Ebolavirus/clasificación , Ebolavirus/genética , Ebolavirus/patogenicidad , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/transmisión , Humanos , Mutación , Filogenia , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , ZoonosisRESUMEN
Viral glycoproteins drive membrane fusion in enveloped viruses and determine host range, tissue tropism and pathogenesis1. Despite their importance, there is a fragmentary understanding of glycoproteins within the Flaviviridae2, a large virus family that include pathogens such as hepatitis C, dengue and Zika viruses, and numerous other human, animal and emergent viruses. For many flaviviruses the glycoproteins have not yet been identified, for others, such as the hepaciviruses, the molecular mechanisms of membrane fusion remain uncharacterized3. Here we combine phylogenetic analyses with protein structure prediction to survey glycoproteins across the entire Flaviviridae. We find class II fusion systems, homologous to the Orthoflavivirus E glycoprotein in most species, including highly divergent jingmenviruses and large genome flaviviruses. However, the E1E2 glycoproteins of the hepaciviruses, pegiviruses and pestiviruses are structurally distinct, may represent a novel class of fusion mechanism, and are strictly associated with infection of vertebrate hosts. By mapping glycoprotein distribution onto the underlying phylogeny, we reveal a complex evolutionary history marked by the capture of bacterial genes and potentially inter-genus recombination. These insights, made possible through protein structure prediction, refine our understanding of viral fusion mechanisms and reveal the events that have shaped the diverse virology and ecology of the Flaviviridae.
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Animals such as raccoon dogs, mink and muskrats are farmed for fur and are sometimes used as food or medicinal products1,2, yet they are also potential reservoirs of emerging pathogens3. Here we performed single-sample metatranscriptomic sequencing of internal tissues from 461 individual fur animals that were found dead due to disease. We characterized 125 virus species, including 36 that were novel and 39 at potentially high risk of cross-species transmission, including zoonotic spillover. Notably, we identified seven species of coronaviruses, expanding their known host range, and documented the cross-species transmission of a novel canine respiratory coronavirus to raccoon dogs and of bat HKU5-like coronaviruses to mink, present at a high abundance in lung tissues. Three subtypes of influenza A virus-H1N2, H5N6 and H6N2-were detected in the lungs of guinea pig, mink and muskrat, respectively. Multiple known zoonotic viruses, such as Japanese encephalitis virus and mammalian orthoreovirus4,5, were detected in guinea pigs. Raccoon dogs and mink carried the highest number of potentially high-risk viruses, while viruses from the Coronaviridae, Paramyxoviridae and Sedoreoviridae families commonly infected multiple hosts. These data also reveal potential virus transmission between farmed animals and wild animals, and from humans to farmed animals, indicating that fur farming represents an important transmission hub for viral zoonoses.
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There is a realistic expectation that the global effort in vaccination will bring the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under control. Nonetheless, uncertainties remain about the type of long-term association that the virus will establish with the human population and, in particular, whether coronavirus disease 2019 (COVID-19) will become an endemic disease. Although the trajectory is difficult to predict, the conditions, concepts and variables that influence this transition can be anticipated. Persistence of SARS-CoV-2 as an endemic virus, perhaps with seasonal epidemic peaks, may be fuelled by pockets of susceptible individuals and waning immunity after infection or vaccination, changes in the virus through antigenic drift that diminish protection and re-entries from zoonotic reservoirs. Here we review relevant observations from previous epidemics and discuss the potential evolution of SARS-CoV-2 as it adapts during persistent transmission in the presence of a level of population immunity. Lack of effective surveillance or adequate response could enable the emergence of new epidemic or pandemic patterns from an endemic infection of SARS-CoV-2. There are key pieces of data that are urgently needed in order to make good decisions; we outline these and propose a way forward.
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COVID-19/epidemiología , COVID-19/virología , Pandemias , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Animales , COVID-19/inmunología , COVID-19/transmisión , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/provisión & distribución , Evolución Molecular , Humanos , Evasión Inmune , Programas de Inmunización , Gripe Humana/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , SARS-CoV-2/inmunología , Factores de TiempoRESUMEN
It is commonly held that there is a fundamental relationship between genome size and error rate, manifest as a notional "error threshold" that sets an upper limit on genome sizes. The genome sizes of RNA viruses, which have intrinsically high mutation rates due to a lack of mechanisms for error correction, must therefore be small to avoid accumulating an excessive number of deleterious mutations that will ultimately lead to population extinction. The proposed exceptions to this evolutionary rule are RNA viruses from the order Nidovirales (such as coronaviruses) that encode error-correcting exonucleases, enabling them to reach genome lengths greater than 40 kb. The recent discovery of large-genome flavi-like viruses (Flaviviridae), which comprise genomes up to 27 kb in length yet seemingly do not encode exonuclease domains, has led to the proposal that a proofreading mechanism is required to facilitate the expansion of nonsegmented RNA virus genomes above 30 kb. Herein, we describe a ~40 kb flavi-like virus identified in a Haliclona sponge metatranscriptome that does not encode a known exonuclease. Structural analysis revealed that this virus may have instead captured cellular domains associated with nucleic acid metabolism that have not been previously found in RNA viruses. Phylogenetic inference placed this virus as a divergent pesti-like lineage, such that we have provisionally termed it "Maximus pesti-like virus." This virus represents an instance of a flavi-like virus achieving a genome size comparable to that of the Nidovirales and demonstrates that RNA viruses have evolved multiple solutions to overcome the error threshold.
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Genoma Viral , Animales , Filogenia , Tamaño del Genoma , Proteínas Virales/genética , Proteínas Virales/metabolismo , Exonucleasas/metabolismo , Exonucleasas/genética , ARN Viral/genéticaRESUMEN
Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
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Betacoronavirus/clasificación , Enfermedades Transmisibles Emergentes/complicaciones , Enfermedades Transmisibles Emergentes/virología , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/virología , Neumonía Viral/complicaciones , Neumonía Viral/virología , Síndrome Respiratorio Agudo Grave/etiología , Síndrome Respiratorio Agudo Grave/virología , Adulto , Betacoronavirus/genética , COVID-19 , China , Enfermedades Transmisibles Emergentes/diagnóstico por imagen , Enfermedades Transmisibles Emergentes/patología , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/patología , Genoma Viral/genética , Humanos , Pulmón/diagnóstico por imagen , Masculino , Filogenia , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/patología , ARN Viral/genética , Recombinación Genética/genética , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/diagnóstico por imagen , Síndrome Respiratorio Agudo Grave/patología , Tomografía Computarizada por Rayos X , Secuenciación Completa del GenomaRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.
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Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Euterios/virología , Evolución Molecular , Genoma Viral/genética , Homología de Secuencia de Ácido Nucleico , Secuencia de Aminoácidos , Animales , Betacoronavirus/química , Betacoronavirus/clasificación , COVID-19 , China/epidemiología , Quirópteros/virología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Reservorios de Enfermedades/virología , Genómica , Humanos , Malasia , Pandemias , Filogenia , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Recombinación Genética , SARS-CoV-2 , Alineación de Secuencia , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Zoonosis/virologíaRESUMEN
The emergence of previously unknown disease-causing viruses in mammals is in part the result of a long-term evolutionary process. Reconstructing the deep phylogenetic histories of viruses helps identify major evolutionary transitions and contextualizes the emergence of viruses in new hosts. We used a combination of total RNA sequencing and transcriptome data mining to extend the diversity and evolutionary history of the RNA virus order Articulavirales, which includes the influenza viruses. We identified instances of Articulavirales in the invertebrate phylum Cnidaria (including corals), constituting a novel and divergent family that we provisionally named the "Cnidenomoviridae." We further extended the evolutionary history of the influenza virus lineage by identifying four divergent, fish-associated influenza-like viruses, thereby supporting the hypothesis that fish were among the first hosts of influenza viruses. In addition, we substantially expanded the phylogenetic diversity of quaranjaviruses and proposed that this genus be reclassified as a family-the "Quaranjaviridae." Within this putative family, we identified a novel arachnid-infecting genus, provisionally named "Cheliceravirus." Notably, we observed a close phylogenetic relationship between the Crustacea- and Chelicerata-infecting "Quaranjaviridae" that is inconsistent with virus-host codivergence. Together, these data suggest that the Articulavirales has evolved over at least 600 million years, first emerging in aquatic animals. Importantly, the evolution of the Articulavirales was likely shaped by multiple aquatic-terrestrial transitions and substantial host jumps, some of which are still observable today.
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Gripe Humana , Orthomyxoviridae , Virus ARN , Animales , Humanos , Filogenia , Virus ARN/genética , Invertebrados/genética , Orthomyxoviridae/genética , ARN , Evolución Molecular , ARN Viral/genética , Mamíferos/genéticaRESUMEN
The production of aquatic animals has more than doubled over the last 50 years and is anticipated to continually increase. While fish are recognized as a valuable and sustainable source of nutrition, particularly in the context of human population growth and climate change, the rapid expansion of aquaculture coincides with the emergence of highly pathogenic viruses that often spread globally through aquacultural practices. Here, we provide an overview of the fish virome and its relevance for disease emergence, with a focus on the insights gained through metagenomic sequencing, noting potential areas for future study. In particular, we describe the diversity and evolution of fish viruses, for which the majority have no known disease associations, and demonstrate how viruses emerge in fish populations, most notably at an expanding domestic-wild interface. We also show how wild fish are a powerful and tractable model system to study virus ecology and evolution more broadly and can be used to identify the major factors that shape vertebrate viromes. Central to this is a process of virus-host co-divergence that proceeds over many millions of years, combined with ongoing cross-species virus transmission.
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Evolución Molecular , Enfermedades de los Peces , Peces , Virus , Animales , Acuicultura/tendencias , Enfermedades de los Peces/transmisión , Enfermedades de los Peces/virología , Peces/clasificación , Peces/virología , Variación Genética , Metagenómica , Filogenia , Viroma/genética , Virosis/transmisión , Virosis/veterinaria , Virosis/virología , Virus/genética , Virus/clasificaciónRESUMEN
Brucellosis is a disease caused by the bacterium Brucella and typically transmitted through contact with infected ruminants. It is one of the most common chronic zoonotic diseases and of particular interest to public health agencies. Despite its well-known transmission history and characteristic symptoms, we lack a more complete understanding of the evolutionary history of its best-known species-Brucella melitensis. To address this knowledge gap we fortuitously found, sequenced and assembled a high-quality ancient B. melitensis draft genome from the kidney stone of a 14th-century Italian friar. The ancient strain contained fewer core genes than modern B. melitensis isolates, carried a complete complement of virulence genes, and did not contain any indication of significant antimicrobial resistances. The ancient B. melitensis genome fell as a basal sister lineage to a subgroup of B. melitensis strains within the Western Mediterranean phylogenetic group, with a short branch length indicative of its earlier sampling time, along with a similar gene content. By calibrating the molecular clock we suggest that the speciation event between B. melitensis and B. abortus is contemporaneous with the estimated time frame for the domestication of both sheep and goats. These results confirm the existence of the Western Mediterranean clade as a separate group in the 14th CE and suggest that its divergence was due to human and ruminant co-migration.
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Brucella melitensis , Brucelosis , Humanos , Animales , Ovinos , Brucella melitensis/genética , Brucella abortus/genética , Filogenia , Brucelosis/microbiología , Zoonosis , CabrasRESUMEN
Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.