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bioRxiv · 10.1101/2023.06.14.544804

Dengue virus preferentially uses human and mosquito non-optimal codons

Castellano, L. A.·McNamara, R. J.·Pallares, H. M.·Gamarnik, A. V.·Alvarez, D. E.·Bazzini, A. A.
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Abstract

Codon optimality refers to the effect codon composition has on messenger RNA (mRNA) stability and translation level and implies that synonymous codons are not silent from a regulatory point of view. Here, we investigated the adaptation of virus genomes to the host optimality code using mosquito-borne dengue virus (DENV) as a model. We defined which codons are associated with unstable and stable (non-optimal and optimal codons, respectively) mRNAs in mosquito cells and showed that DENV preferentially uses non-optimal codons and avoids codons that are defined as optimal in either human or mosquito cells. Human genes enriched in the codons preferentially and frequently used by DENV are up-regulated during infection, and so is the tRNA decoding the non-optimal and DENV preferentially used codon for arginine. We found that synonymous mutations towards DENVs preferred non-optimal codons (e.g., AGA) increase fitness of DENV during serial passaging in human or mosquito cells. Finally, our analyses revealed that hundreds of viruses preferentially use non-optimal codons, with those infecting a single host displaying an even stronger bias, suggesting that synonymous codon choice is a key aspect of host-pathogen interaction.

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Castellano, L. A., McNamara, R. J., Pallares, H. M., Gamarnik, A. V., Alvarez, D. E., Bazzini, A. A.. 2023-06-14. Dengue virus preferentially uses human and mosquito non-optimal codons. https://doi.org/10.1101/2023.06.14.544804

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