#Bat-Origin #Coronaviruses Expand Their #Host Range to #Pigs (Front Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Trends Microbiol. 2018 Jun;26(6):466-470. doi: 10.1016/j.tim.2018.03.001. Epub 2018 Apr 18.

Bat-Origin Coronaviruses Expand Their Host Range to Pigs.

Wang L1, Su S2, Bi Y3, Wong G4, Gao GF5.

Author information: 1 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China. 2 MOE Joint International Research Laboratory of Animal Health and Food Safety, Jiangsu Engineering Laboratory of Animal Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. 3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China; Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen 518112, China. 4 Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen 518112, China. 5 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China; Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen 518112, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: gaof@im.ac.cn.

 

Abstract

Infections with bat-origin coronaviruses have caused severe illness in humans by ‘host jump’. Recently, novel bat-origin coronaviruses were found in pigs. The large number of mutations on the receptor-binding domain allowed the viruses to infect the new host, posing a potential threat to both agriculture and public health.

Copyright © 2018 Elsevier Ltd. All rights reserved.

KEYWORDS: SeACoV; bat-origin; host jump; public health; swine enteric alphacoronaviruses

PMID: 29680361 DOI: 10.1016/j.tim.2018.03.001 [Indexed for MEDLINE]

Keywords: Coronavirus; Bats; Pigs; Alphacoronavirus.

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#Human #coronaviruses #OC43 and #HKU1 bind to 9-O-acetylated #sialic acids via a conserved receptor-binding site in spike protein domain A (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A

Ruben J. G. Hulswit, Yifei Lang, Mark J. G. Bakkers, Wentao Li, Zeshi Li, Arie Schouten, Bram Ophorst, Frank J. M. van Kuppeveld, Geert-Jan Boons, Berend-Jan Bosch, Eric G. Huizinga, and Raoul J. de Groot

PNAS published ahead of print January 24, 2019 / DOI: https://doi.org/10.1073/pnas.1809667116

Edited by Mary K. Estes, Baylor College of Medicine, Houston, TX, and approved December 19, 2018 (received for review June 6, 2018)

 

Significance

Human coronaviruses OC43 and HKU1 are related, yet distinct respiratory pathogens, associated with common colds, but also with severe disease in the frail. Both viruses employ sialoglycan-based receptors with 9-O-acetylated sialic acid (9-O-Ac-Sia) as key component. Here, we identify the 9-O-Ac-Sia–specific receptor-binding site of OC43 S and demonstrate it to be conserved and functional in HKU1. The considerable difference in receptor-binding affinity between OC43 and HKU1 S, attributable to differences in local architecture and receptor-binding site accessibility, is suggestive of differences between OC43 and HKU1 in their adaptation to the human sialome. The data will enable studies into the evolution and pathobiology of OC43 and HKU1 and open new avenues toward prophylactic and therapeutic intervention.

 

Abstract

Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species Betacoronavirus-1, and more closely related to bovine coronavirus (BCoV)—its presumptive ancestor—and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9-O-acetylated sialic acid (9-O-Ac-Sia). Receptor binding is mediated by spike protein S, the main determinant of coronavirus host specificity. For BCoV, a crystal structure for the receptor-binding domain S1A is available and for HKU1 a cryoelectron microscopy structure of the complete S ectodomain. However, the location of the receptor-binding site (RBS), arguably the single-most important piece of information, is unknown. Here we solved the 3.0-Å crystal structure of PHEV S1A. We then took a comparative structural analysis approach to map the β1CoV S RBS, using the general design of 9-O-Ac-Sia-binding sites as blueprint, backed-up by automated ligand docking, structure-guided mutagenesis of OC43, BCoV, and PHEV S1A, and infectivity assays with BCoV-S–pseudotyped vesicular stomatitis viruses. The RBS is not exclusive to OC43 and related animal viruses, but is apparently conserved and functional also in HKU1 S1A. The binding affinity of the HKU1 S RBS toward short sialoglycans is significantly lower than that of OC43, which we attribute to differences in local architecture and accessibility, and which may be indicative for differences between the two viruses in receptor fine-specificity. Our findings challenge reports that would map the OC43 RBS elsewhere in S1A and that of HKU1 in domain S1B.

coronavirus – spike – 9-O-acetylated sialic acid – OC43 – HKU1

 

Footnotes

1 R.J.G.H., Y.L., and M.J.G.B. contributed equally to this work.

2 Present address: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.

3 To whom correspondence should be addressed. Email: r.j.degroot@uu.nl.

Author contributions: R.J.G.H. and M.J.G.B conceived the study; R.J.d.G. coordinated and supervised the study; R.J.G.H., Y.L., M.J.G.B., W.L., E.G.H., and R.J.d.G. designed research; R.J.G.H., Y.L., M.J.G.B., A.S., B.O., and E.G.H. performed research; W.L., Z.L., G.-J.B., and B.-J.B. contributed new reagents/analytic tools; R.J.G.H. and A.S. performed crystallization experiments; M.J.G.B., Y.L., and E.G.H. refined the PHEV S1A structure and performed automated ligand docking; Y.L. established assays to detect HKU1 S receptor binding and performed infection experiments with pseudotyped vesicular stomatitis virus; E.G.H. supervised crystal structure analysis; R.J.G.H., Y.L., M.J.G.B., W.L., Z.L., A.S., F.J.M.v.K., G.-J.B., B.-J.B., E.G.H., and R.J.d.G. analyzed data; M.J.G.B. performed in silico structural analysis to identify the RBS; and R.J.G.H., Y.L., M.J.G.B., E.G.H., and R.J.d.G. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.wwpdb.org (PDB ID code 6QFY). The amino acid sequences of the S1A–Fc fusion proteins were deposited in the GenBank database (accession no. MG999832-35).

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1809667116/-/DCSupplemental.

Published under the PNAS license.

Keywords: Coronavirus; Betacoronavirus; HCoV-OC43; HCoV-HKU1; Viral pathogenesis.

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What Have We Learned About #MERS #Coronavirus Emergence in #Humans? A Systematic Literature #Review (Vector Borne Zoo Dis., abstract)

[Source: Vector Borne and Zoonotic Diseases, full page: (LINK). Abstract, edited.]

What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review

Patrick Dawson, Mamunur Rahman Malik, Faruque Parvez, and Stephen S. Morse

Published Online: 24 Jan 2019 / DOI: https://doi.org/10.1089/vbz.2017.2191

 

Abstract

Background:

Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps.

Materials and Methods:

We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV.

Results:

Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials.

Conclusions:

There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as “camel exposure” and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified “One Health” approach.

Keywords: MERS-CoV; Coronavirus; Human; Camels; Bats; Vaccines.

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From #SARS to #MERS, Thrusting #Coronaviruses into the Spotlight (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2019 Jan 14;11(1). pii: E59. doi: 10.3390/v11010059.

From SARS to MERS, Thrusting Coronaviruses into the Spotlight.

Song Z1,2,3, Xu Y4,5,6, Bao L7,8,9, Zhang L10,11,12, Yu P13,14,15, Qu Y16,17,18, Zhu H19,20,21, Zhao W22,23,24, Han Y25,26,27, Qin C28,29,30.

Author information: 1 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. songzhiqi1989@foxmail.com. 2 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. songzhiqi1989@foxmail.com. 3 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. songzhiqi1989@foxmail.com. 4 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. xuyanf2009@163.com. 5 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. xuyanf2009@163.com. 6 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. xuyanf2009@163.com. 7 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. bllmsl@aliyun.com. 8 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. bllmsl@aliyun.com. 9 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. bllmsl@aliyun.com. 10 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. zhangling@cnilas.org. 11 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. zhangling@cnilas.org. 12 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. zhangling@cnilas.org. 13 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. pinyucau@gmail.com. 14 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. pinyucau@gmail.com. 15 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. pinyucau@gmail.com. 16 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. quyj@cnilas.org. 17 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. quyj@cnilas.org. 18 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. quyj@cnilas.org. 19 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. zhuh@cnilas.org. 20 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. zhuh@cnilas.org. 21 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. zhuh@cnilas.org. 22 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. hnndwenjiezhao@163.com. 23 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. hnndwenjiezhao@163.com. 24 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. hnndwenjiezhao@163.com. 25 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. 18510165683@163.com. 26 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. 18510165683@163.com. 27 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. 18510165683@163.com. 28 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. qinchuan@pumc.edu.cn. 29 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. qinchuan@pumc.edu.cn. 30 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. qinchuan@pumc.edu.cn.

 

Abstract

Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.

KEYWORDS: MERS-CoV; SARS-CoV; animal model; coronaviruses; prevention and treatment; spike proteins

PMID: 30646565 DOI: 10.3390/v11010059

Keywords: MERS-CoV; SARS; Coronavirus.

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Acute #respiratory #infection in #human #DPP4-transgenic mice infected with #MERS #coronavirus (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Acute respiratory infection in human dipeptidyl peptidase 4-transgenic mice infected with Middle East respiratory syndrome coronavirus

Naoko Iwata-Yoshikawa, Tadashi Okamura, Yukiko Shimizu, Osamu Kotani, Hironori Sato, Hanako Sekimukai, Shuetsu Fukushi, Tadaki Suzuki, Yuko Sato, Makoto Takeda, Masato Tashiro,Hideki Hasegawa, Noriyo Nagata

DOI: 10.1128/JVI.01818-18

 

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On Day 5 or 7 post-inoculation, lungs of adult Tg mice contained higher levels of pro-inflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS infection in the Tg mouse is age-dependent. The mouse model described herein will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection.

 

IMPORTANCE

Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human (h)DPP4. The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Coronavirus; MERS-CoV; Animal models; Viral pathogenesis.

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TMPRSS2 contributes to #virus spread and #immunopathology in the #airways of murine models after #coronavirus infection (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection

Naoko Iwata-Yoshikawa, Tadashi Okamura, Yukiko Shimizu, Hideki Hasegawa, Makoto Takeda, Noriyo Nagata

DOI: 10.1128/JVI.01815-18

 

ABSTRACT

Transmembrane serine protease TMPRSS2 activates the spike protein of highly pathogenic human coronaviruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV). In vitro, activation induces virus-cell membrane fusion at the cell surface. However, the roles of TMPRSS2 during coronavirus infection in vivo are unclear. Here, we used animal models of SARS-CoV and MERS-CoV infection to investigate the role of TMPRSS2. Th-1-prone C57BL/6 mice and TMPRSS2-knockout (KO) mice were used for SARS-CoV infection, and transgenic mice expressing the human MERS-CoV receptor, hDPP4-Tg mice, and TMPRSS2-KO hDPP4-Tg mice were used for MERS-CoV infection. After experimental infection, TMPRSS2-deficient mouse strains showed reduced body weight loss and viral kinetics in the lungs. Lack of TMPRSS2 affected the primary sites of infection and virus spread within the airway, accompanied by less severe immunopathology. However, TMPRSS2-KO mice showed weakened inflammatory chemokine and/or cytokine responses to intranasal stimulation with poly (I:C), a Toll-like receptor 3 agonist. In conclusion, TMPRSS2 plays a crucial role in viral spread within the airway of murine models infected by SARS-CoV and MERS-CoV and in the resulting immunopathology.

 

IMPORTANCE

Broad-spectrum antiviral drugs against highly pathogenic coronaviruses and other emerging viruses are desirable to enable a rapid response to pandemic threats. Transmembrane protease serine type2 (TMPRSS2), a protease belonging to the type II transmembrane serine protease family, cleaves the coronavirus spike protein, making it a potential therapeutic target for coronavirus infections. Here, we examined the role of TMPRSS2 using animal models of SARS-CoV and MERS-CoV infection. The results suggest that lack of TMPRSS2 in the airways reduces the severity of lung pathology after infection by SARS-CoV and MERS-CoV. Taken together, the results will facilitate development of novel targets for coronavirus therapy.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Coronavirus; MERS-CoV; SARS; Viral pathogenesis.

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Identification and characterization of #Coronaviridae #genomes from #Vietnamese #bats and rats based on conserved protein domains (Virus Evol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virus Evol. 2018 Dec 15;4(2):vey035. doi: 10.1093/ve/vey035. eCollection 2018 Jul.

Identification and characterization of Coronaviridae genomes from Vietnamese bats and rats based on conserved protein domains.

Phan MVT1,2, Ngo Tri T3, Hong Anh P3, Baker S3, Kellam P4,5, Cotten M1,2.

Author information: 1 Virus Genomics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. 2 Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands. 3 Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. 4 Department of Infection and Immunity, Imperial College London, London, UK. 5 Kymab Ltd, Babraham Research Campus, Cambridge, UK.

 

Abstract

The Coronaviridae family of viruses encompasses a group of pathogens with a zoonotic potential as observed from previous outbreaks of the severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. Accordingly, it seems important to identify and document the coronaviruses in animal reservoirs, many of which are uncharacterized and potentially missed by more standard diagnostic assays. A combination of sensitive deep sequencing technology and computational algorithms is essential for virus surveillance, especially for characterizing novel- or distantly related virus strains. Here, we explore the use of profile Hidden Markov Model-defined Pfam protein domains (Pfam domains) encoded by new sequences as a Coronaviridae sequence classification tool. The encoded domains are used first in a triage to identify potential Coronaviridae sequences and then processed using a Random Forest method to classify the sequences to the Coronaviridae genus level. The application of this algorithm on Coronaviridae genomes assembled from agnostic deep sequencing data from surveillance of bats and rats in Dong Thap province (Vietnam) identified thirty-four Alphacoronavirus and eleven Betacoronavirus genomes. This collection of bat and rat coronaviruses genomes provided essential information on the local diversity of coronaviruses and substantially expanded the number of coronavirus full genomes available from bat and rats and may facilitate further molecular studies on this group of viruses.

KEYWORDS: Pfam; machine learning; profile Hidden Markov model; protein domains; random forest; virus classification

PMID: 30568804 PMCID: PMC6295324 DOI: 10.1093/ve/vey035

Keywords: Coronavirus; Alphacoronavirus; Betacoronavirus; Bats; Vietnam.

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