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Evolution of the coronavirus spike protein in the full-length genome and defective viral genome under diverse selection pressures.

ABSTRACT: How coronaviruses evolve by altering the structures of their full-length genome and defective viral genome (DVG) under dynamic selection pressures has not been studied. In this study, we aimed to experimentally identify the dynamic evolutionary patterns of the S protein sequence in the full-length genome and DVG under diverse selection pressures, including persistence, innate immunity and antiviral drugs. The evolutionary features of the S protein sequence in the full-length genome and in the DVG under diverse selection pressures are as follows: (i) the number of nucleotide (nt) mutations does not necessarily increase with the number of selection pressures; (ii) certain types of selection pressure(s) can lead to specific nt mutations; (iii) the mutated nt sequence can be reverted to the wild-type nt sequence under the certain type of selection pressure(s); (iv) the DVG can also undergo mutations and evolve independently of the full-length genome; and (v) DVG species are regulated during evolution under diverse selection pressures. The various evolutionary patterns of the S protein sequence in the full-length genome and DVG identified in this study may contribute to coronaviral fitness under diverse selection pressures.

SUBMITTER: Lin CH

PROVIDER: S-EPMC10768696 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Evolution of the coronavirus spike protein in the full-length genome and defective viral genome under diverse selection pressures.

Lin Ching-Hung CH Tam Hon-Man-Herman HM Yang Cheng-Yao CY Hsieh Feng-Cheng FC Wang Jiun-Long JL Yang Chun-Chun CC Hsu Hsuan-Wei HW Liu Hao-Ping HP Wu Hung-Yi HY

The Journal of general virology 20231101 11

How coronaviruses evolve by altering the structures of their full-length genome and defective viral genome (DVG) under dynamic selection pressures has not been studied. In this study, we aimed to experimentally identify the dynamic evolutionary patterns of the S protein sequence in the full-length genome and DVG under diverse selection pressures, including persistence, innate immunity and antiviral drugs. The evolutionary features of the S protein sequence in the full-length genome and in the DV ...[more]

PMID: 37997889

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Project description:BackgroundThe mechanism by which coronavirus-defective viral genomes (DVGs) affect coronavirus and host cells during infection remains unclear. A variety of DVGs with different RNA structures can be synthesized from coronavirus-infected cells, and these DVGs can also encode proteins. Consequently, in the present study, we first dissected the effects of individual DVGs on the synthesis of IFNβ and ISG15 mRNAs at the RNA, protein and combined levels, and then examined whether different coronavirus-DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions.MethodsTo dissect the effects of individual DVGs on the synthesis of IFNβ and ISG15 mRNAs at the RNA, protein and combined levels, DVG 2.2 and DVG 5.1, which were previously identified in coronavirus-infected cells, and their mutants were constructed followed by transfection. Western blot and RT‒qPCR were used to detect the synthesis of protein and to quantify the synthesis of IFNβ and ISG15 mRNAs, respectively. To examined whether different coronavirus-DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions, different naturally occurring DVGs were selected and constructed followed by transfection after or before coronavirus infection and by RT‒qPCR and hemagglutination assay.ResultsThese results suggested that (i) coronavirus-DVGs at the RNA, protein and combined levels have different effects on the synthesis of IFNβ and ISG15 mRNAs, (ii) coronavirus-DVGs can inhibit coronavirus replication at least partly through interferon signaling and (iii) different DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions.ConclusionsCoronavirus replication can be regulated by diverse coronavirus-derived DVGs at least partly through innate immunity. Such regulation may contribute to the pathogenesis of coronavirus. The DVG populations in coronavirus-infected cells with the ability to inhibit coronavirus replication are expected to be potential resources for the identification of antivirals at the level of RNA, protein or in combination, and the methods used in the current study can be used as a platform for this purpose.

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Evolution of the coronavirus spike protein in the full-length genome and defective viral genome under diverse selection pressures.

Publications

Evolution of the coronavirus spike protein in the full-length genome and defective viral genome under diverse selection pressures.

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