The battle against  SARS  and  MERS  coronaviruses: Reservoirs and Animal Models

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Abstract

In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus ( SARS‐CoV) and the emerging Middle East respiratory syndrome coronavirus ( MERS‐CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.

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Most cited references 32

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Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

Theo M. Bestebroer, Albert Osterhaus, Sander van Boheemen … (2012)

A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.

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Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats.

S K P Lau, P Woo, K. S. M. Li … (2005)

Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals.

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Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus.

P Woo, S K P Lau, C. S. F. Lam … (2012)

Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination.

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Author and article information

Contributors

Lin‐lin Bao: bllmsl@aliyun.com

Journal

Journal ID (nlm-ta): Animal Model Exp Med

Journal ID (iso-abbrev): Animal Model Exp Med

Journal ID (doi): 10.1002/(ISSN)2576-2095

Journal ID (publisher-id): AME2

Title: Animal Models and Experimental Medicine

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 2096-5451

ISSN (Electronic): 2576-2095

Publication date (Electronic): 28 July 2018

Publication date Collection: June 2018

Volume: 1

Issue: 2 ( doiID: 10.1002/ame2.2018.1.issue-2 )

Pages: 125-133

Affiliations

[ ¹ ] Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center Peking Union Medical College (PUMC) Key Laboratory of Human Disease Comparative Medicine Ministry of Health Key Laboratory for Animal Models of Emerging and Reemerging Infectious Beijing China

Author notes

[*] [* ] Correspondence

Lin‐lin Bao, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China.

Email: bllmsl@ 123456aliyun.com

Article

Publisher ID: AME212017

DOI: 10.1002/ame2.12017

PMC ID: 6388065

PubMed ID: 30891557

SO-VID: 4fbea81f-0896-4b15-a51c-92acd2d36b2c

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date received : 28 February 2018

Date accepted : 24 April 2018

Page count

Figures: 0, Tables: 1, Pages: 9, Words: 6325

Funding

Funded by: National Key Research and Development Project of China

Award ID: 2016YFD0500304

Funded by: CAMS Innovation Fund for Medical Sciences

Award ID: 2016‐I2M‐1‐014\2016‐12M‐006

Funded by: Chinese National Major S & T Project

Award ID: 2017ZX10304402‐001‐003

Custom metadata

source-schema-version-number 2.0

component-id ame212017

cover-date June 2018

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.0 mode:remove_FC converted:25.02.2019

Keywords: animal models,coronaviruses,reservoirs,the middle east respiratory syndrome (canonical form),the severe acute respiratory syndrome

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Keywords: animal models, coronaviruses, reservoirs, the middle east respiratory syndrome (canonical form), the severe acute respiratory syndrome

The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models

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Abstract

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Microbiology Society: Coronaviruses

Most cited references 32

Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats.

Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus.

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