PT  - JOURNAL ARTICLE
AU  - Castellano, Luciana A
AU  - McNamara, Ryan J
AU  - Pallares, Horacio M
AU  - Gamarnik, Andrea V
AU  - Alvarez, Diego E
AU  - Bazzini, Ariel A
TI  - Dengue virus preferentially uses human and mosquito non-optimal codons
AID  - 10.1101/2023.06.14.544804
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.06.14.544804
4099  - http://biorxiv.org/content/early/2023/06/14/2023.06.14.544804.short
4100  - http://biorxiv.org/content/early/2023/06/14/2023.06.14.544804.full
AB  - 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 DENV’s 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.Competing Interest StatementThe authors have declared no competing interest.