The Roles of APOBEC-mediated RNA Editing in SARS-CoV-2 Mutations, Replication and Fitness

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• SARS-CoV-2 mutations drive new strains, impacting infectivity and vaccine efficacy.
• Viral RNA mutations originate from polymerase errors and host factor modifications.
• A C-to-U mutation bias in SARS-CoV-2 suggests a role for host APOBEC cytosine deaminases.

Approach:

• Experimental demonstration of APOBEC3A, APOBEC1, and APOBEC3G editing SARS-CoV-2 RNA.
• Analysis of viral replication and progeny production in Caco-2 cells with APOBEC expression.
• Investigation of APOBEC-mediated mutation patterns and their correlation with viral fitness.

Key Points:

• APOBEC3A, APOBEC1, and APOBEC3G experimentally confirmed to induce C-to-U mutations in SARS-CoV-2 RNA.
• Contrary to expectations, APOBEC expression does not inhibit but significantly promotes SARS-CoV-2 replication and propagation.
• SARS-CoV-2 appears to leverage APOBEC-mediated mutations for viral fitness and evolutionary adaptation.

Conclusions:

• The study provides the first experimental evidence of APOBECs editing SARS-CoV-2 RNA, leading to C-to-U mutations.
• SARS-CoV-2 utilizes APOBEC-mediated mutations for enhanced replication and evolution, rather than being inhibited by them.
• Viral genome mutations induced by APOBECs are predictable based on UC/AC motifs and RNA structure, offering insights into viral evolution.