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REVIEW article

Front. Microbiol.

Sec. Virology

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1711603

Viral codon usage and the virus-host interactions

Provisionally accepted
Thanyaporn  SirihongthongThanyaporn Sirihongthong1,2Prasert  AuewarakulPrasert Auewarakul1,2*
  • 1Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • 2Emerging Infectious Diseases Research Unit, Research department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

The final, formatted version of the article will be published soon.

Codon usage pattern is a specific characteristic of each species as a result of evolution and interaction between genome composition and translational machinery. Species-specific optimal codon usage is a requirement for efficient expression in cells of that species. Viruses pose a curious situation where their genomes must interact with their hosts. Codon usage and genome composition of most viruses infecting eukaryotic hosts are markedly different from those of their hosts. How these viruses efficiently express their genes with non-optimal codon usage is not well understood. Some evidence suggests that they may manipulate host translational machinery to achieve this. On the other hand, host cells may launch innate antiviral defense to suppress expression of viral genes with non-optimal codon usage. Codon usages of viruses are more similar among viruses within the same genome type. This suggests that there may be common mechanisms driving codon usage of viruses within the same genome type. These interactions may contribute to host adaptation in inter-species transmission and viral emergence. However, direct adaptation to be more similar with host codon usage pattern is not always the case. Complex viral-host interaction may direct evolution of viral codon usage. More understanding in these interactions may provide new insight into the viral evolution and host adaptation and offer new possibilities in fighting against new and old viruses. Here we review various aspects of these interactions.

Keywords: viral codon usage, virus-host interactions, codon-specific translation, TRNA modification, wobble-base pairing, Antiviral target

Received: 23 Sep 2025; Accepted: 21 Oct 2025.

Copyright: © 2025 Sirihongthong and Auewarakul. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prasert Auewarakul, prasert.aue@mahidol.ac.th

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