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SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists

The Coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2 virus, is now causing a tremendous global health concern. Since its first appearance in December 2019, the outbreak has already caused over 5.8 million infections worldwide (till 29 May 2020), with more than 0.35 millio...

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Autores principales: Yuen, Chun-Kit, Lam, Joy-Yan, Wong, Wan-Man, Mak, Long-Fung, Wang, Xiaohui, Chu, Hin, Cai, Jian-Piao, Jin, Dong-Yan, To, Kelvin Kai-Wang, Chan, Jasper Fuk-Woo, Yuen, Kwok-Yung, Kok, Kin-Hang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473193/
https://www.ncbi.nlm.nih.gov/pubmed/32529952
http://dx.doi.org/10.1080/22221751.2020.1780953
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author Yuen, Chun-Kit
Lam, Joy-Yan
Wong, Wan-Man
Mak, Long-Fung
Wang, Xiaohui
Chu, Hin
Cai, Jian-Piao
Jin, Dong-Yan
To, Kelvin Kai-Wang
Chan, Jasper Fuk-Woo
Yuen, Kwok-Yung
Kok, Kin-Hang
author_facet Yuen, Chun-Kit
Lam, Joy-Yan
Wong, Wan-Man
Mak, Long-Fung
Wang, Xiaohui
Chu, Hin
Cai, Jian-Piao
Jin, Dong-Yan
To, Kelvin Kai-Wang
Chan, Jasper Fuk-Woo
Yuen, Kwok-Yung
Kok, Kin-Hang
author_sort Yuen, Chun-Kit
collection PubMed
description The Coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2 virus, is now causing a tremendous global health concern. Since its first appearance in December 2019, the outbreak has already caused over 5.8 million infections worldwide (till 29 May 2020), with more than 0.35 million deaths. Early virus-mediated immune suppression is believed to be one of the unique characteristics of SARS-CoV-2 infection and contributes at least partially to the viral pathogenesis. In this study, we identified the key viral interferon antagonists of SARS-CoV-2 and compared them with two well-characterized SARS-CoV interferon antagonists, PLpro and orf6. Here we demonstrated that the SARS-CoV-2 nsp13, nsp14, nsp15 and orf6, but not the unique orf8, could potently suppress primary interferon production and interferon signalling. Although SARS-CoV PLpro has been well-characterized for its potent interferon-antagonizing, deubiquitinase and protease activities, SARS-CoV-2 PLpro, despite sharing high amino acid sequence similarity with SARS-CoV, loses both interferon-antagonising and deubiquitinase activities. Among the 27 viral proteins, SARS-CoV-2 orf6 demonstrated the strongest suppression on both primary interferon production and interferon signalling. Orf6-deleted SARS-CoV-2 may be considered for the development of intranasal live-but-attenuated vaccine against COVID-19.
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spelling pubmed-74731932020-09-15 SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists Yuen, Chun-Kit Lam, Joy-Yan Wong, Wan-Man Mak, Long-Fung Wang, Xiaohui Chu, Hin Cai, Jian-Piao Jin, Dong-Yan To, Kelvin Kai-Wang Chan, Jasper Fuk-Woo Yuen, Kwok-Yung Kok, Kin-Hang Emerg Microbes Infect Articles The Coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2 virus, is now causing a tremendous global health concern. Since its first appearance in December 2019, the outbreak has already caused over 5.8 million infections worldwide (till 29 May 2020), with more than 0.35 million deaths. Early virus-mediated immune suppression is believed to be one of the unique characteristics of SARS-CoV-2 infection and contributes at least partially to the viral pathogenesis. In this study, we identified the key viral interferon antagonists of SARS-CoV-2 and compared them with two well-characterized SARS-CoV interferon antagonists, PLpro and orf6. Here we demonstrated that the SARS-CoV-2 nsp13, nsp14, nsp15 and orf6, but not the unique orf8, could potently suppress primary interferon production and interferon signalling. Although SARS-CoV PLpro has been well-characterized for its potent interferon-antagonizing, deubiquitinase and protease activities, SARS-CoV-2 PLpro, despite sharing high amino acid sequence similarity with SARS-CoV, loses both interferon-antagonising and deubiquitinase activities. Among the 27 viral proteins, SARS-CoV-2 orf6 demonstrated the strongest suppression on both primary interferon production and interferon signalling. Orf6-deleted SARS-CoV-2 may be considered for the development of intranasal live-but-attenuated vaccine against COVID-19. Taylor & Francis 2020-06-20 /pmc/articles/PMC7473193/ /pubmed/32529952 http://dx.doi.org/10.1080/22221751.2020.1780953 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Yuen, Chun-Kit
Lam, Joy-Yan
Wong, Wan-Man
Mak, Long-Fung
Wang, Xiaohui
Chu, Hin
Cai, Jian-Piao
Jin, Dong-Yan
To, Kelvin Kai-Wang
Chan, Jasper Fuk-Woo
Yuen, Kwok-Yung
Kok, Kin-Hang
SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
title SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
title_full SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
title_fullStr SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
title_full_unstemmed SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
title_short SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
title_sort sars-cov-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473193/
https://www.ncbi.nlm.nih.gov/pubmed/32529952
http://dx.doi.org/10.1080/22221751.2020.1780953
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