Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction.
Identifieur interne : 000971 ( 2020/Analysis ); précédent : 000970; suivant : 000972Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction.
Auteurs : Siu-Ying Lau [République populaire de Chine] ; Pui Wang [République populaire de Chine] ; Bobo Wing-Yee Mok [République populaire de Chine] ; Anna Jinxia Zhang [République populaire de Chine] ; Hin Chu [République populaire de Chine] ; Andrew Chak-Yiu Lee [République populaire de Chine] ; Shaofeng Deng [République populaire de Chine] ; Pin Chen [République populaire de Chine] ; Kwok-Hung Chan [République populaire de Chine] ; Wenjun Song [République populaire de Chine] ; Zhiwei Chen [République populaire de Chine] ; Kelvin Kai-Wang To [République populaire de Chine] ; Jasper Fuk-Woo Chan [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine] ; Honglin Chen [République populaire de Chine]Source :
- Emerging microbes & infections [ 2222-1751 ] ; 2020.
Abstract
The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect this variant. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30 bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variant as an attenuated vaccine or laboratory tool should be evaluated.
DOI: 10.1080/22221751.2020.1756700
PubMed: 32301390
Affiliations:
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SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Pin" sort="Chen, Pin" uniqKey="Chen P" first="Pin" last="Chen">Pin Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 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Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Pui" sort="Wang, Pui" uniqKey="Wang P" first="Pui" last="Wang">Pui Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Mok, Bobo Wing Yee" sort="Mok, Bobo Wing Yee" uniqKey="Mok B" first="Bobo Wing-Yee" last="Mok">Bobo Wing-Yee Mok</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Anna Jinxia" sort="Zhang, Anna Jinxia" uniqKey="Zhang A" first="Anna Jinxia" last="Zhang">Anna Jinxia Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Andrew Chak Yiu" sort="Lee, Andrew Chak Yiu" uniqKey="Lee A" first="Andrew Chak-Yiu" last="Lee">Andrew Chak-Yiu Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Deng, Shaofeng" sort="Deng, Shaofeng" uniqKey="Deng S" first="Shaofeng" last="Deng">Shaofeng Deng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Pin" sort="Chen, Pin" uniqKey="Chen P" first="Pin" last="Chen">Pin Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author></analytic><series><title level="j">Emerging microbes & infections</title><idno type="eISSN">2222-1751</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect this variant. Infection of hamsters shows that one of the variants (Del-mut-1) which <b>carries</b> deletion of 10 amino acids (30 bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variant as an attenuated vaccine or laboratory tool should be evaluated.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Lau, Siu Ying" sort="Lau, Siu Ying" uniqKey="Lau S" first="Siu-Ying" last="Lau">Siu-Ying Lau</name></noRegion><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><name sortKey="Chen, Pin" sort="Chen, Pin" uniqKey="Chen P" first="Pin" last="Chen">Pin Chen</name><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><name sortKey="Deng, Shaofeng" sort="Deng, Shaofeng" uniqKey="Deng S" first="Shaofeng" last="Deng">Shaofeng Deng</name><name sortKey="Lee, Andrew Chak Yiu" sort="Lee, Andrew Chak Yiu" uniqKey="Lee A" first="Andrew Chak-Yiu" last="Lee">Andrew Chak-Yiu Lee</name><name sortKey="Mok, Bobo Wing Yee" sort="Mok, Bobo Wing Yee" uniqKey="Mok B" first="Bobo Wing-Yee" last="Mok">Bobo Wing-Yee Mok</name><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name><name sortKey="To, Kelvin Kai Wang" sort="To, Kelvin Kai Wang" uniqKey="To K" first="Kelvin Kai-Wang" last="To">Kelvin Kai-Wang To</name><name sortKey="Wang, Pui" sort="Wang, Pui" uniqKey="Wang P" first="Pui" last="Wang">Pui Wang</name><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><name sortKey="Zhang, Anna Jinxia" sort="Zhang, Anna Jinxia" uniqKey="Zhang A" first="Anna Jinxia" last="Zhang">Anna Jinxia Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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