Dengue virus preferentially uses human and mosquito non-optimal codons.

Autor: Castellano LA; Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO, 64110, USA., McNamara RJ; Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO, 64110, USA., Pallarés HM; Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO, 64110, USA.; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina., Gamarnik AV; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires IIBBA-CONICET, Ciudad Autónoma de Buenos Aires, Argentina., Alvarez DE; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín-CONICET, San Martín B1650, Argentina., Bazzini AA; Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO, 64110, USA. arb@stowers.org.; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA. arb@stowers.org.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2024 Oct; Vol. 20 (10), pp. 1085-1108. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.1038/s44320-024-00052-7
Abstrakt: Codon optimality refers to the effect that 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 demonstrated that codon optimality exists in mosquito cells and showed that DENV preferentially uses nonoptimal (destabilizing) codons and avoids codons that are defined as optimal (stabilizing) in either human or mosquito cells. Human genes enriched in the codons preferentially and frequently used by DENV are upregulated during infection, and so is the tRNA decoding the nonoptimal and DENV preferentially used codon for arginine. We found that adaptation during single-host passaging in human or mosquito cells results in the selection of synonymous mutations towards DENV's preferred nonoptimal codons that increase virus fitness. Finally, our analyses revealed that hundreds of viruses preferentially use nonoptimal codons, with those infecting a single host displaying an even stronger bias, suggesting that host-pathogen interaction shapes virus-synonymous codon choice.
(© 2024. The Author(s).)
Databáze: MEDLINE
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