Differential RNA editing landscapes in host cell versus the SARS-CoV-2 genome

The SARS-CoV-2 pandemic was defined by the emergence of new variants formed through virus mutation originating from random errors not corrected by viral proofreading and/or the host antiviral response introducing mutations into the viral genome. While sequencing information hints at cellular RNA edi...

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Published iniScience Vol. 26; no. 11; p. 108031
Main Authors Kurkowiak, Małgorzata, Fletcher, Sarah, Daniels, Alison, Mozolewski, Paweł, Silvestris, Domenico Alessandro, Król, Ewelina, Marek-Trzonkowska, Natalia, Hupp, Ted, Tait-Burkard, Christine
Format Journal Article
LanguageEnglish
Published Elsevier Inc 17.11.2023
Elsevier
Subjects
Evolutionary biology
Virology
Evolutionary biology
Virology
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Abstract The SARS-CoV-2 pandemic was defined by the emergence of new variants formed through virus mutation originating from random errors not corrected by viral proofreading and/or the host antiviral response introducing mutations into the viral genome. While sequencing information hints at cellular RNA editing pathways playing a role in viral evolution, here, we use an in vitro human cell infection model to assess RNA mutation types in two SARS-CoV-2 strains representing the original and the alpha variants. The variants showed both different cellular responses and mutation patterns with alpha showing higher mutation frequency with most substitutions observed being C-U, indicating an important role for apolipoprotein B mRNA editing catalytic polypeptide-like editing. Knockdown of select APOBEC3s through RNAi increased virus production in the original virus, but not in alpha. Overall, these data suggest a deaminase-independent anti-viral function of APOBECs in SARS-CoV-2 while the C-U editing itself might function to enhance genetic diversity enabling evolutionary adaptation. [Display omitted] •RNA-modifying enzymes are upregulated upon SARS-CoV-2 infection in vitro•SARS-CoV-2 VOC Alpha shows a significant increase of C-U RNA edits•Knockdown of APOBEC3B and 3D increases virus replication of original SARS-CoV-2•Effect of APOBEC3B and 3D knockdown disappears in VOCs Alpha, Delta, and Omicron Virology; Evolutionary biology
AbstractList The SARS-CoV-2 pandemic was defined by the emergence of new variants formed through virus mutation originating from random errors not corrected by viral proofreading and/or the host antiviral response introducing mutations into the viral genome. While sequencing information hints at cellular RNA editing pathways playing a role in viral evolution, here, we use an in vitro human cell infection model to assess RNA mutation types in two SARS-CoV-2 strains representing the original and the alpha variants. The variants showed both different cellular responses and mutation patterns with alpha showing higher mutation frequency with most substitutions observed being C-U, indicating an important role for apolipoprotein B mRNA editing catalytic polypeptide-like editing. Knockdown of select APOBEC3s through RNAi increased virus production in the original virus, but not in alpha. Overall, these data suggest a deaminase-independent anti-viral function of APOBECs in SARS-CoV-2 while the C-U editing itself might function to enhance genetic diversity enabling evolutionary adaptation.
The SARS-CoV-2 pandemic was defined by the emergence of new variants formed through virus mutation originating from random errors not corrected by viral proofreading and/or the host antiviral response introducing mutations into the viral genome. While sequencing information hints at cellular RNA editing pathways playing a role in viral evolution, here, we use an in vitro human cell infection model to assess RNA mutation types in two SARS-CoV-2 strains representing the original and the alpha variants. The variants showed both different cellular responses and mutation patterns with alpha showing higher mutation frequency with most substitutions observed being C-U, indicating an important role for apolipoprotein B mRNA editing catalytic polypeptide-like editing. Knockdown of select APOBEC3s through RNAi increased virus production in the original virus, but not in alpha. Overall, these data suggest a deaminase-independent anti-viral function of APOBECs in SARS-CoV-2 while the C-U editing itself might function to enhance genetic diversity enabling evolutionary adaptation. [Display omitted] •RNA-modifying enzymes are upregulated upon SARS-CoV-2 infection in vitro•SARS-CoV-2 VOC Alpha shows a significant increase of C-U RNA edits•Knockdown of APOBEC3B and 3D increases virus replication of original SARS-CoV-2•Effect of APOBEC3B and 3D knockdown disappears in VOCs Alpha, Delta, and Omicron Virology; Evolutionary biology
The SARS-CoV-2 pandemic was defined by the emergence of new variants formed through virus mutation originating from random errors not corrected by viral proofreading and/or the host antiviral response introducing mutations into the viral genome. While sequencing information hints at cellular RNA editing pathways playing a role in viral evolution, here, we use an in vitro human cell infection model to assess RNA mutation types in two SARS-CoV-2 strains representing the original and the alpha variants. The variants showed both different cellular responses and mutation patterns with alpha showing higher mutation frequency with most substitutions observed being C-U, indicating an important role for apolipoprotein B mRNA editing catalytic polypeptide-like editing. Knockdown of select APOBEC3s through RNAi increased virus production in the original virus, but not in alpha. Overall, these data suggest a deaminase-independent anti-viral function of APOBECs in SARS-CoV-2 while the C-U editing itself might function to enhance genetic diversity enabling evolutionary adaptation. • RNA-modifying enzymes are upregulated upon SARS-CoV-2 infection in vitro • SARS-CoV-2 VOC Alpha shows a significant increase of C-U RNA edits • Knockdown of APOBEC3B and 3D increases virus replication of original SARS-CoV-2 • Effect of APOBEC3B and 3D knockdown disappears in VOCs Alpha, Delta, and Omicron Virology; Evolutionary biology
ArticleNumber 108031
Author Mozolewski, Paweł
Daniels, Alison
Silvestris, Domenico Alessandro
Kurkowiak, Małgorzata
Król, Ewelina
Marek-Trzonkowska, Natalia
Tait-Burkard, Christine
Fletcher, Sarah
Hupp, Ted
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  article-title: From RNA World to SARS-CoV-2: The Edited Story of RNA Viral Evolution
  publication-title: Cells
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Title Differential RNA editing landscapes in host cell versus the SARS-CoV-2 genome
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