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tRNA Modifications: A Tale of Two Viruses-SARS-CoV-2 and ZIKV
Patrick Eldin1, Laurence Briant1
1Institut de Recherche en Infectiologie de Montpellier (IRIM), University of Montpellier, CNRS UMR 9004, 1919 Route de Mende, 34293 Montpellier, France.
International Journal of Molecular Sciences
|August 14, 2025
Summary
Viruses like SARS-CoV-2 and Zika virus manipulate host transfer RNA (tRNA) modifications, specifically U34 wobble modifications. This strategy ensures efficient viral protein synthesis by overcoming codon usage differences and supporting viral replication.
Area of Science:
- Molecular Biology
- Virology
- Genetics
Background:
- Transfer RNA (tRNA) modifications are essential for accurate and efficient protein synthesis.
- RNA viruses utilize host cell machinery, including modified tRNAs, for their own protein production.
- Viral and host codon usage often differs, potentially causing translational challenges for viruses.
Purpose of the Study:
- To investigate how SARS-CoV-2 and Zika virus (ZIKV) manage translational challenges arising from codon usage mismatches.
- To determine if these viruses manipulate the host tRNA epitranscriptome to optimize viral protein synthesis.
Main Methods:
- Analysis of codon bias indices in viral genomes.
- Monitoring of tRNA modification levels in infected host cells.
- Experimental manipulation of U34 tRNA function to assess impact on viral replication.
Main Results:
- SARS-CoV-2 and ZIKV genomes show a preference for codons decoded by tRNAs dependent on U34 wobble modification.
- Both viruses were observed to enhance U34 tRNA modifications during infection.
- Disruption of U34 tRNA function significantly hindered the replication of both SARS-CoV-2 and ZIKV.
Conclusions:
- SARS-CoV-2 and ZIKV viruses actively manipulate the host tRNA epitranscriptome, particularly U34 modifications.
- This manipulation is crucial for overcoming codon bias and ensuring efficient viral genome translation and replication.
- Targeting tRNA epitranscriptome modifications presents a potential avenue for antiviral strategies.
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