ArticlePublisher preview available

Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin

To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health1. Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS)2-10. Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.
This content is subject to copyright. Terms and conditions apply.
Fatal swine acute diarrhoea syndrome caused by an
HKU2-related coronavirus of bat origin
Peng Zhou1,12, Hang Fan2,12, Tian Lan3,4,12, Xing-Lou Yang1, Wei-Feng Shi5, Wei Zhang1, Yan Zhu1, Ya-Wei Zhang2, Qing-Mei
Xie3,4, Shailendra Mani6, Xiao-Shuang Zheng1, Bei Li1, Jin-Man Li2, Hua Guo1, Guang-Qian Pei2, Xiao-Ping An2, Jun-Wei Chen3,4,
Ling Zhou3,4, Kai-Jie Mai3,4, Zi-Xian Wu3,4, Di Li3,4, Danielle E. Anderson6, Li-Biao Zhang7, Shi-Yue Li8, Zhi-Qiang Mi2,
Tong-Tong He2, Feng Cong9, Peng-Ju Guo9, Ren Huang9, Yun Luo1, Xiang-Ling Liu1, Jing Chen1, Yong Huang2, Qiang Sun2,
Xiang-Li-Lan Zhang2, Yuan-Yuan Wang2, Shao-Zhen Xing2, Yan-Shan Chen3,4, Yuan Sun3,4, Juan Li5, Peter Daszak10*,
Lin-Fa Wang6*, Zheng-Li Shi1*, Yi-Gang Tong2,11* & Jing-Yun Ma3,4*
Cross-species transmission of viruses from wildlife animal
reservoirs poses a marked threat to human and animal health1.
Bats have been recognized as one of the most important reservoirs
for emerging viruses and the transmission of a coronavirus
that originated in bats to humans via intermediate hosts was
responsible for the high-impact emerging zoonosis, severe acute
respiratory syndrome (SARS)2–10. Here we provide virological,
epidemiological, evolutionary and experimental evidence that
a novel HKU2-related bat coronavirus, swine acute diarrhoea
syndrome coronavirus (SADS-CoV), is the aetiological agent that
was responsible for a large-scale outbreak of fatal disease in pigs in
China that has caused the death of 24,693 piglets across four farms.
Notably, the outbreak began in Guangdong province in the vicinity
of the origin of the SARS pandemic. Furthermore, we identified
SADS-related CoVs with 96–98% sequence identity in 9.8% (58 out
of 591) of anal swabs collected from bats in Guangdong province
during 2013–2016, predominantly in horseshoe bats (Rhinolophus
spp.) that are known reservoirs of SARS-related CoVs. We found
that there were striking similarities between the SADS and SARS
outbreaks in geographical, temporal, ecological and aetiological
settings. This study highlights the importance of identifying
coronavirus diversity and distribution in bats to mitigate future
outbreaks that could threaten livestock, public health and economic
The emergence of SARS in southern China in 2002, which was
caused by a previously unknown coronavirus (SARS-CoV)
has led to more than 8,000 human infections and 774 deaths (http://, highlights two new frontiers in emerging
infectious diseases. First, it demonstrates that coronaviruses are capable
of causing fatal diseases in humans. Second, the identification of bats as
the reservoir for SARS-related coronaviruses, and the fact that SARS-
CoV3–10 probably originated in bats, firmly establishes that bats are an
important source of highly lethal zoonotic viruses, such as Hendra,
Nipah, Ebola and Marburg viruses16.
Here we report on a series of fatal swine disease outbreaks in
Guangdong province, China, approximately 100 km from the location
of the purported index case of SARS. Most strikingly, we found that
the causative agent of this swine acute diarrhoea syndrome (SADS) is
a novel HKU2-related coronavirus that is 98.48% identical in genome
sequence to a bat coronavirus, which we detected in 2016 in bats in a
cave in the vicinity of the index pig farm. This new virus (SADS-CoV)
originated from the same genus of horseshoe bats (Rhinolophus) as
From 28 October 2016 onwards, a fatal swine disease outbreak was
observed in a pig farm in Qingyuan, Guangdong province, China,
very close to the location of the first known index case of SARS in
2002, who lived in Foshan (Extended Data Fig.1a). Porcine epidemic
diarrhoea virus (PEDV, a coronavirus) had caused prior outbreaks at
this farm, and was detected in the intestines of deceased piglets at the
start of the outbreak. However, PEDV could no longer be detected in
deceased piglets after 12 January 2017, despite accelerating mortality
(Fig.1a), and extensive testing for other common swine viruses yielded
no results (Extended Data Table1). These findings suggested that this
was an outbreak of a novel disease. Clinical signs are similar to those
caused by other known swine enteric coronaviruses
and include
severe and acute diarrhoea and acute vomiting, leading to death due
to rapid weight loss in newborn piglets that are less than five days of
age. Infected piglets died 2–6 days after disease onset, whereas infected
sows suffered only mild diarrhoea and most sows recovered within
two days. The disease caused no signs of febrile illness in piglets or
sows. The mortality rate was as high as 90% in piglets that were five
days or younger, whereas in piglets that were older than eight days, the
mortality dropped to 5%. Subsequently, SADS-related outbreaks were
found in three additional pig farms within 20–150 km of the index farm
(Extended Data Fig.1a) and, by 2 May 2017, the disease had caused
the death of 24,693 piglets at these four farms (Fig.1a). In farm A
alone, 64% (4,659 out of 7,268) of all piglets that were born in February
died. The outbreak has abated, and measures that were taken to control
SADS included separation of sick sows and piglets from the rest of the
herd. A qPCR test described below was used as the main diagnostic
tool to confirm SADS-CoV infection.
A sample collected from the small intestine of a diseased piglet was
analysed by metagenomics analysis using next-generation sequenc-
ing (NGS) to identify potential aetiological agents. Of the 15,256,565
total reads obtained, 4,225 matched sequences of the bat CoV HKU2,
which was first detected in Chinese horseshoe bats in Hong Kong and
Guangdong province, China19. By de novo assembly and targeted PCR,
we obtained a 27,173-bp CoV genome that shared 95% sequence iden-
tity to HKU2-CoV (GenBank accession number NC_009988). Thirty-
three full genome sequences of SADS-CoV were subsequently obtained
(8 from farm A, 5 from farm B, 11 from farm C and 9 from farm D) that
were 99.9% identical to each other (Supplementary Table1).
1CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. 2Beijing Institute of Microbiology and Epidemiology, Beijing,
China. 3College of Animal Science, South China Agricultural University, Guangzhou, China. 4Key Laboratory of Animal Health Aquaculture and Environmental Control, Guangzhou, China.
5KeyLaboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Taian, China. 6Programme in Emerging Infectious Diseases,
Duke-NUS Medical School, Singapore, Singapore. 7Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and
Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, China. 8School of Public Health, Wuhan University, Wuhan, China. 9Guangdong Key Laboratory of Laboratory Animals,
Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China. 10EcoHealth Alliance, New York, NY, USA. 11School of Life Sciences, North China University of Science and Technology,
Tangshan, China. 12These authors contributed equally: Peng Zhou, Hang Fan, Tian Lan. *e-mail:;;; tong.yigang@gmail.
12 APRIL 2018 | VOL 556 | NATURE | 255
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Content courtesy of Springer Nature, terms of use apply. Rights reserved
... Porcine epidemic diarrhea virus is considered to be more pathogenic than PDCoV, and the mortality rates of PEDV and PDCoV in newborn piglets are about 80-100% and 40%, respectively (Jung et al. 2016; Niederwerder and Hesse 2018). In China, SADS-CoV mortality was high (90-100%) in piglets younger than 5 days old, but it was reduced to 5% in piglets older than 8 days (Zhou et al. 2018;Xu et al. 2019). ...
... During 2017 in Southern China, a unique bat-HKU2like pig coronavirus (GDSO4 strain), i.e. porcine enteric Alphacoronavirus (PEAV), causing severe diarrhea in suckling piglets was reported (Gong et al. 2017). It was later known as swine acute diarrhea syndrome CoV (SADS-CoV) (Zhou et al. 2018). ...
... Swine acute diarrhea syndrome coronavirus strain sequence resembles the HKU2 coronavirus of Rhinolophus spp. bats, implying that SADS-CoV may have originated from bats (Zhou et al. 2018). ...
Full-text available
Swine coronaviruses (SCoVs) are one of the most devastating pathogens affecting the livelihoods of farmers and swine industry across the world. These include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine respiratory coronavirus (PRCV), porcine hemagglutinating encephalomyelitis virus (PHEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and porcine delta coronavirus (PDCoV). Coronavirses infect a wide variety of animal species and humans because these are having single stranded-RNA that accounts for high mutation rates and thus could break the species barrier. The gastrointestinal, cardiovascular, and nervous systems are the primary organ systems affected by SCoVs. Infection is usually very common in piglets compared to adult pigs causing high mortality. Bat is implicated to be the origin of all CoVs affecting animals and humans. Since pig is the only domestic animal in which CoVs cause a wide range of diseases; new coronaviruses with high zoonotic potential could likely emerge in the future as observed in the past. The recently emerged severe acute respiratory syndrome coronavirus virus-2 (SARS-CoV-2), causing COVID-19 pandemic in humans, has been implicated to have animal origin, also reported from few animal species, though it’s zoonotic concerns are under investigations. This review discusses SCoVs and their epidemiology, virology, evolution, pathology, wildlife reservoirs, interspecies transmission, spill-over events and highlighting their emerging threats to swine population. The role of pigs amid ongoing SARS-CoV-2 pandemic has also been discussed. A thorough investigation should be conducted to rule out zoonotic potential of SCoVs and to design appropriate strategies for their prevention and control.
... CoVs can also have devastating effects in livestock populations, particularly pigs. CoVs with swine health implications include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome virus (SADS-CoV), among others 1,16,17 . The Deltacoronavirus genus comprises mostly avian CoV pathogens of songbirds including HKU11 (bulbul coronavirus), HKU12 (thrush coronavirus), and HKU13 (munia coronavirus) 18 . ...
... This disease is caused by a novel strain of Rhinolophus bat coronavirus HKU2 1,17 . Zhou et al., provided significant evidence that the causative agent of SADS-CoV is a novel HKU2-related coronavirus that has 98.48% identity in genome sequence to HKU2 17 . ...
Full-text available
Coronaviruses are important viral pathogens across a range of animal species including humans. They have a high potential for cross-species transmission as evidenced by the emergence of COVID-19 and may be the origin of future pandemics. There is therefore an urgent need to study coronaviruses in depth and to identify new therapeutic targets. This study shows that distant coronaviruses such as Alpha-, Beta-, and Deltacoronaviruses can share common host immune associated pathways and genes. Differentially expressed genes (DEGs) in the transcription profile of epithelial cell lines infected with swine acute diarrhea syndrome, severe acute respiratory syndrome coronavirus 2, or porcine deltacoronavirus, showed that DEGs within 10 common immune associated pathways were upregulated upon infection. Twenty Three pathways and 21 DEGs across 10 immune response associated pathways were shared by these viruses. These 21 DEGs can serve as focused targets for therapeutics against newly emerging coronaviruses. We were able to show that even though there is a positive correlation between PDCoV and SARS-CoV-2 infections, these viruses could be using different strategies for efficient replication in their cells from their natural hosts. To the best of our knowledge, this is the first report of comparative host transcriptome analysis across distant coronavirus genres.
... Therefore, these results showed that circovirus can maintain a certain degree of virulence in feces and can infect other animals through the fecal-oral route. Phylogenetic analysis showed that PCV3 has a close relationship with birds and penguins (Figure 3), which suggests that the transmission mode of circovirus might be similar to that of influenza, in which birds play a crucial role as the intermediate host (Zhou et al., 2018;Karakus et al., 2019;Wang et al., 2020). However, in this cycle, whether the source of porcine circovirus is directly transmitted by birds and/or wild boars is worthy of further analysis. ...
... Therefore, in the future, attention must be paid to the possibility of PCV3 transmission within different species. Transmission of PCV3 in different hosts may be a risk for public safety, similar to the recently identified bat-originating coronavirus found in pigs Zhou et al., 2018). ...
Full-text available
Porcine circovirus type 3 (PCV3) is a newly identified virus associated with porcine dermatitis and nephropathy syndrome (PDNS) and multisystemic inflammatory responses in pigs. Recent studies suggests that PCV3 originated from bat circoviruses; however, the origin time, mode of spread, and geographic distribution of PCV3 remain unclear. In this study, the evolutionary origin, phylodynamics, and phylogeography of PCV3 were reconstructed based on the available complete genome sequences. PCV3 showed a closer relationship with bird circovirus than with bat circovirus, but their common ancestor was bat circovirus, indicating that birds may be intermediate hosts for the spread of circoviruses in pigs. Using the BEAST and phylogenetic analyses, three different clades of PCV3 (PCV3a, PCV3b, and PCV3c) were identified, with PCV3a being the most prevalent PCV3 clade. Further studies indicated that the earliest origin of PCV3 can be traced back to 1907.53–1923.44, with a substitution rate of 3.104 × 10–4 to 6.8524 × 10–4 substitution/site/year. A phylogeographic analysis highlighted Malaysia as the earliest location of the original PCV3, which migrated to Asia, America, and Europe. Overall, this study provides novel insights into the evolutionary origin, spread mode, and geographic distribution of PCV3, which will facilitate the prevention and control of PCV3 epidemics in the future.
... Accumulating evidence also suggests that other emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory coronavirus (MERS-CoV), also have bat origins 3 . Another emerging coronavirus, swine acute diarrhea syndrome coronavirus, emerged from horseshoe bats and killed many pigs 4 . The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) further underscores the ongoing threat of bat-borne virus spillover 5 . ...
Full-text available
Bats are considered reservoirs of many lethal zoonotic viruses and have been implicated in several outbreaks of emerging infectious diseases, such as SARS-CoV, MERS-CoV, and SARS-CoV-2. It is necessary to systematically derive the expression patterns of bat virus receptors and their regulatory features for future research into bat-borne viruses and the prediction and prevention of pandemics. Here, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) of major organ samples collected from Chinese horseshoe bats (Rhinolophus affinis) and systematically checked the expression pattern of bat-related virus receptors and chromatin accessibility across organs and cell types, providing a valuable dataset for studying the nature of infection among bat-borne viruses. Measurement(s)RNA-seq gene expression profiling assay • ATAC-SeqTechnology Type(s)RNA-seq of coding RNA from single cells • Single cell ATAC-seq (cell index)Sample Characteristic - OrganismRhinolophus affinis Measurement(s) RNA-seq gene expression profiling assay • ATAC-Seq Technology Type(s) RNA-seq of coding RNA from single cells • Single cell ATAC-seq (cell index) Sample Characteristic - Organism Rhinolophus affinis
... The recent deployment of pathogen discovery technology has identified several epidemics or local outbreaks of emerging pathogens, such as Reston ebolavirus [14] and swine acute diarrhea syndrome coronavirus [15,16]. These pathogens most likely originated in one mammalian species (such as bats) and were introduced into pigs via cross-species transmission; thus, they also have the potential to infect humans [17]. ...
Full-text available
Background The global pork industry is continuously affected by infectious diseases that can result in large-scale mortality, trade restrictions, and major reductions in production. Nevertheless, the cause of many infectious diseases in pigs remains unclear, largely because commonly used diagnostic tools fail to capture the full diversity of potential pathogens and because pathogen co-infection is common. Results We used a meta-transcriptomic approach to systematically characterize the pathogens in 136 clinical cases representing different disease syndromes in pigs, as well as in 12 non-diseased controls. This enabled us to simultaneously determine the diversity, abundance, genomic information, and detailed epidemiological history of a wide range of potential pathogens. We identified 34 species of RNA viruses, nine species of DNA viruses, seven species of bacteria, and three species of fungi, including two novel divergent members of the genus Pneumocystis . While most of these pathogens were only apparent in diseased animals or were at higher abundance in diseased animals than in healthy animals, others were present in healthy controls, suggesting opportunistic infections. Importantly, most of the cases examined here were characterized by co-infection with more than two species of viral, bacterial, or fungal pathogens, some with highly correlated occurrence and abundance levels. Examination of clinical signs and necropsy results in the context of relevant pathogens revealed that a multiple-pathogen model was better associated with the data than a single-pathogen model was. Conclusions Our data demonstrate that most of the pig diseases examined were better explained by the presence of multiple rather than single pathogens and that infection with one pathogen can facilitate infection or increase the prevalence/abundance of another. Consequently, it is generally preferable to consider the cause of a disease based on a panel of co-infecting pathogens rather than on individual infectious agents.
Multiple domestic and wild animal species are susceptible to SARS-CoV-2 infection. Cattle and swine are susceptible to experimental SARS-CoV-2 infection. The unchecked transmission of SARS-CoV-2 in animal hosts could lead to virus adaptation and the emergence of novel variants. In addition, the spillover and subsequent adaptation of SARS-CoV-2 in livestock could significantly impact food security as well as animal and public health. Therefore, it is essential to monitor livestock species for SARS-CoV-2 spillover. We developed and optimized species-specific indirect ELISAs (iELISAs) to detect anti-SARS-CoV-2 antibodies in cattle, swine, and chickens using the spike protein receptor-binding domain (RBD) antigen. Serum samples collected prior to the COVID-19 pandemic were used to determine the cut-off threshold. RBD hyperimmunized sera from cattle (n = 3), swine (n = 6), and chicken (n = 3) were used as the positive controls. The iELISAs were evaluated compared to a live virus neutralization test using cattle (n = 150), swine (n = 150), and chicken (n = 150) serum samples collected during the COVID-19 pandemic. The iELISAs for cattle, swine, and chicken were found to have 100% sensitivity and specificity. These tools facilitate the surveillance that is necessary to quickly identify spillovers into the three most important agricultural species worldwide.
Intestinal microbial metabolites have been increasingly recognized as important regulators of enteric viral infection. However, very little information is available about which specific microbiota-derived metabolites are crucial for swine enteric coronavirus (SECoV) infection in vivo. Using swine acute diarrhea syndrome (SADS)-CoV as a model, we were able to identify a greatly altered bile acid (BA) profile in the small intestine of infected piglets by untargeted metabolomic analysis. Using a newly established ex vivo model-the stem cell-derived porcine intestinal enteroid (PIE) culture-we demonstrated that certain BAs, cholic acid (CA) in particular, enhance SADS-CoV replication by acting on PIEs at the early phase of infection. We ruled out the possibility that CA exerts an augmenting effect on viral replication through classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling, innate immune suppression or viral attachment. BA induced multiple cellular responses including rapid changes in caveolae-mediated endocytosis, endosomal acidification and dynamics of the endosomal/lysosomal system that are critical for SADS-CoV replication. Thus, our findings shed light on how SECoVs exploit microbiome-derived metabolite BAs to swiftly establish viral infection and accelerate replication within the intestinal microenvironment.
Full-text available
The Chapter has discussed the Neurological Perspective of Covid-19.
Porcine bocavirus (PBoV) was first identified in Sweden in 2009. Due to its association with healthy as well as diseased pigs, its role in clinical disease has not been reported yet. In the present study, bocavirus was identified from the intestinal content of a 30-day-old piglet and its whole genome was constructed and phylogenetic analysis was carried on. The pathogenesis of bocavirus was investigated following orogastric inoculation of the colostrum-deprived newborn piglet with bacteria free intestinal content. The bocavirus-inoculated piglets developed diarrhea, shed virus in the rectal swabs from 18 hours post inoculation and developed macroscopic and microscopic lesions in small intestine with virus confirmed by conventional PCR. This study experimentally confirmed pathogenicity and characterized bocavirus as the etiological agent of diarrhea in the colostrum-deprived newborn piglets. On phylogenetic analysis, it was observed that this virus has long evolutionary history with subsequent mutation as well as better host adaptation. This study highlights the importance of identifying bocavirus as the etiological agent of viral diarrhea that could threaten livestock, public health as well as economic loss.
Full-text available
A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.
Full-text available
We identified from suckling piglets with diarrhea in China a new bat-HKU2–like porcine coronavirus (porcine enteric alphacoronavirus). The GDS04 strain of this coronavirus shares high aa identities (>90%) with the reported bat-HKU2 strains in Coronaviridae-wide conserved domains, suggesting that the GDS04 strain belongs to the same species as HKU2.
Full-text available
The majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, HIV, Ebola and SARS). Understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. However, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species boundaries. Here we conduct a comprehensive analysis of mammalian host-virus relationships and show that both the total number of viruses that infect a given species and the proportion likely to be zoonotic are predictable. After controlling for research effort, the proportion of zoonotic viruses per species is predicted by phylogenetic relatedness to humans, host taxonomy and human population within a species range-which may reflect human-wildlife contact. We demonstrate that bats harbour a significantly higher proportion of zoonotic viruses than all other mammalian orders. We also identify the taxa and geographic regions with the largest estimated number of 'missing viruses' and 'missing zoonoses' and therefore of highest value for future surveillance. We then show that phylogenetic host breadth and other viral traits are significant predictors of zoonotic potential, providing a novel framework to assess if a newly discovered mammalian virus could infect people.
Full-text available
To investigate bat coronaviruses (CoVs), we collected 132 rectal swabs and urine samples from five bat species in three countries in southwestern China. Seven CoVs belonging to distinct groups of severe acute respiratory syndrome (SARS)-like CoVs and α-CoVs were detected in samples from least horseshoe bats. Samples from other bat species were negative for these viruses, indicating that the least horseshoe bat represents one of the natural reservoirs and mixers for strains of CoVs and has a pivotal role in the evolution and dissemination of these viruses. The genetic and evolutionary characteristics of these strains were described. Whole-genome sequencing of a new isolate (F46) from a rectal swab from a least horseshoe bat showed that it contained 29 699 nucleotides, excluding the poly (A) tail, with 13 open reading frames (ORFs). Phylogenetic and recombination analyses of F46 provided evidence of natural recombination between bat SARS-like CoVs (Rs3367 and LYRa11) or SARS-CoV (BJ01), suggesting that F46 could be a new recombinant virus from SARS-like CoVs or SARS-CoVs.
Full-text available
Wereport the isolation and characterization of a novel bat coronavirus which is much closer to the severe acute respiratory syndrome coronavirus (SARS-CoV) in genomic sequence than others previously reported, particularly in its S gene. Cell entry and susceptibility studies indicated that this virus can use ACE2 as a receptor and infect animal and human cell lines. Our results provide further evidence of the bat origin of the SARS-CoV and highlight the likelihood of future bat coronavirus emergence in humans.
Full-text available
Porcine epidemic diarrhea (PED) is an intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV); manifestations of the disease are diarrhea, vomiting and dehydration. Starting from the end of 2010, a PED outbreak occurred in several pig-producing provinces in southern China. Subsequently, the disease spread throughout the country and caused enormous economic losses to the pork industry. Accumulating studies demonstrated that new PEDV variants that appeared in China were responsible for the PED outbreak. In the current mini-review, we summarize PEDV epidemiology and vaccination in China.
Full-text available
Several lineage B betacoronaviruses termed Severe Acute Respiratory Syndrome (SARS) - like CoVs (SL-CoVs) were identified from Rhinolophus bats in China. These viruses are characterized by a set of Unique Accessory ORFs (UA-ORFs) that are located between the M and N genes. Among UA-ORFs, ORF8 is most hyper-variable. In this study, we classified the ORF8s of all SL-CoVs into three types and found for the first time that very few SL-CoVs from R. sinicus have ORF8s that are identical to that of human SARS-CoV. This finding provides new genetic evidence for Chinese horseshoe bats as the source of human SARS-CoV.
Full-text available
Unlabelled: Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been identified in bats in China, Europe, and Africa, most have a genetic organization significantly distinct from human/civet SARS CoVs in the receptor-binding domain (RBD), which mediates receptor binding and determines the host spectrum, resulting in their failure to cause human infections and making them unlikely progenitors of human/civet SARS CoVs. Here, a viral metagenomic analysis of 268 bat rectal swabs collected from four counties in Yunnan Province has identified hundreds of sequences relating to alpha- and betacoronaviruses. Phylogenetic analysis based on a conserved region of the RNA-dependent RNA polymerase gene revealed that alphacoronaviruses had diversities with some obvious differences from those reported previously. Full genomic analysis of a new SARS-like CoV from Baoshan (LYRa11) showed that it was 29,805 nucleotides (nt) in length with 13 open reading frames (ORFs), sharing 91% nucleotide identity with human/civet SARS CoVs and the most recently reported SARS-like CoV Rs3367, while sharing 89% with other bat SARS-like CoVs. Notably, it showed the highest sequence identity with the S gene of SARS CoVs and Rs3367, especially in the RBD region. Antigenic analysis showed that the S1 domain of LYRa11 could be efficiently recognized by SARS-convalescent human serum, indicating that LYRa11 is a novel virus antigenically close to SARS CoV. Recombination analyses indicate that LYRa11 is likely a recombinant descended from parental lineages that had evolved into a number of bat SARS-like CoVs. Importance: Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been discovered in bats worldwide, there are significant different genic structures, particularly in the S1 domain, which are responsible for host tropism determination, between bat SARS-like CoVs and human SARS CoVs, indicating that most reported bat SARS-like CoVs are not the progenitors of human SARS CoV. We have identified diverse alphacoronaviruses and a close relative (LYRa11) to SARS CoV in bats collected in Yunnan, China. Further analysis showed that alpha- and betacoronaviruses have different circulation and transmission dynamics in bat populations. Notably, full genomic sequencing and antigenic study demonstrated that LYRa11 is phylogenetically and antigenically closely related to SARS CoV. Recombination analyses indicate that LYRa11 is a recombinant from certain bat SARS-like CoVs circulating in Yunnan Province.
Outbreaks of diarrhea in newborn piglets without detection of transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), have been recorded in a pig farm in southern China since February 2017. Isolation and propagation of the pathogen in cell culture resulted in discovery of a novel swine enteric alphacoronavirus (tentatively named SeACoV) related to the bat coronavirus HKU2 identified in the same region a decade ago. Specific fluorescence signal was detected in Vero cells infected with SeACoV by using a positive sow serum collected in the same farm, but not by using TGEV-, PEDV- or PDCoV-specific antibody. Electron microscopy observation demonstrated that the virus particle with surface projections was 100–120 nm in diameter. Complete genomic sequencing and analyses of SeACoV indicated that the extreme amino-terminal domain of the SeACoV spike (S) glycoprotein structurally similar to the domain 0 of the alphacoronavirus NL63, whereas the rest part of S structurally resembles domains B to D of the betacoronavirus. The SeACoV-S domain 0 associated with enteric tropism had an extremely high variability, harboring 75-amino-acid (aa) substitutions and a 2-aa insertion, compared to that of HKU2, which is likely responsible for the extended host range or cross-species transmission. The isolated virus was infectious in pigs when inoculated orally into 3-day-old newborn piglets, leading to clinical signs of diarrhea and fecal virus shedding. These results confirmed that it is a novel swine enteric coronavirus representing the fifth porcine coronavirus.