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

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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.
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LETTER https://doi.org/10.1038/s41586-018-0010-9
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
growth.
The emergence of SARS in southern China in 2002, which was
caused by a previously unknown coronavirus (SARS-CoV)
1115
and
has led to more than 8,000 human infections and 774 deaths (http://
www.who.int/csr/sars/en/), 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
SARS-CoV.
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
17,18
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: daszak@ecohealthalliance.org; linfa.wang@duke-nus.edu.sg; zlshi@wh.iov.cn; tong.yigang@gmail.
com; majy2400@scau.edu.cn
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
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