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Journal Articles Journal of Biological Chemistry Year : 2022

Replication of the coronavirus genome: A paradox among positive-strand RNA viruses

Abstract

Coronavirus (CoV) genomes consist of positive-sense single- stranded RNA and are among the largest viral RNAs known to date (30 kb). As a result, CoVs deploy sophisticated mecha- nisms to replicate these extraordinarily large genomes as well as to transcribe subgenomic messenger RNAs. Since 2003, with the emergence of three highly pathogenic CoVs (SARS-CoV, MERS-CoV, and SARS-CoV-2), significant progress has been made in the molecular characterization of the viral proteins and key mechanisms involved in CoV RNA genome replication. For example, to allow for the maintenance and integrity of their large RNA genomes, CoVs have acquired RNA proofreading 30- 50 exoribonuclease activity (in nonstructural protein nsp14). In order to replicate the large genome, the viral-RNA–dependent RNA polymerase (RdRp; in nsp12) is supplemented by a processivity factor (made of the viral complex nsp7/nsp8), making it the fastest known RdRp. Lastly, a viral structural protein, the nucleocapsid (N) protein, which is primarily involved in genome encapsidation, is required for efficient viral replication and transcription. Therefore, CoVs are a paradox among positive-strand RNA viruses in the sense that they use both a processivity factor and have proofreading activity reminiscent of DNA organisms in addition to structural pro- teins that mediate efficient RNA synthesis, commonly used by negative-strand RNA viruses. In this review, we present a his- torical perspective of these unsuspected discoveries and detail the current knowledge on the core replicative machinery deployed by CoVs.
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hal-03856707 , version 1 (16-11-2022)

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Emeline Grellet, India l'Hôte, Adeline Goulet, Isabelle Imbert. Replication of the coronavirus genome: A paradox among positive-strand RNA viruses. Journal of Biological Chemistry, 2022, 298, ⟨10.1016/j.jbc.2022.101923⟩. ⟨hal-03856707⟩
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