The Roles of APOBEC-mediated RNA Editing in SARS-CoV-2 Mutations, Replication and Fitness.
bioRxiv
; 2022 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-34981048
ABSTRACT
During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A, APOBEC1, and APOBEC3G can edit on specific sites of SARS-CoV-2 RNA to produce C-to-U mutations. However, SARS-CoV-2 replication and viral progeny production in Caco-2 cells are not inhibited by the expression of these APOBECs. Instead, expression of wild-type APOBEC3 greatly promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the random mutations, this study suggests the predictability of all possible viral genome mutations by these APOBECs based on the UC/AC motifs and the viral genomic RNA structure. ONE-SENTENCE SUMMARY:
Efficient Editing of SARS-CoV-2 genomic RNA by Host APOBEC deaminases and Its Potential Impacts on the Viral Replication and Emergence of New Strains in COVID-19 Pandemic.
Texto completo:
1
Bases de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
BioRxiv
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos