RT Journal Article
SR Electronic
T1 Dengue virus preferentially uses human and mosquito non-optimal codons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.06.14.544804
DO 10.1101/2023.06.14.544804
A1 Castellano, Luciana A
A1 McNamara, Ryan J
A1 Pallares, Horacio M
A1 Gamarnik, Andrea V
A1 Alvarez, Diego E
A1 Bazzini, Ariel A
YR 2023
UL http://biorxiv.org/content/early/2023/06/14/2023.06.14.544804.abstract
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.