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Emerg Microbes Infect. Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction

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  • Emerg Microbes Infect. Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction


    Emerg Microbes Infect. 2020 Apr 17:1-15. doi: 10.1080/22221751.2020.1756700. [Epub ahead of print]
    Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction.


    Lau SY1, Wang P1, Mok BW1, Zhang AJ1, Chu H1, Lee AC1, Deng S1, Chen P1, Chan KH1,2, Song W1, Chen Z1, To KK1, Chan JF1, Yuen KY1, Chen H1.

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    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.



    PMID:32301390DOI:10.1080/22221751.2020.1756700

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