{"doi":"10.1101/2023.06.14.544804","title":"Dengue virus preferentially uses human and mosquito non-optimal codons","abstract":"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 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":408630,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.966,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1188260,"name":"Ryan J McNamara","orcid":null,"position":1,"is_corresponding":false},{"id":329885,"name":"Horacio M. Pallarés","orcid":"0000-0002-2019-8574","position":2,"is_corresponding":false},{"id":297193,"name":"Andrea V. Gamarnik","orcid":"0000-0002-9789-4105","position":3,"is_corresponding":false},{"id":642537,"name":"Diego E. Álvarez","orcid":"0000-0002-4449-9670","position":4,"is_corresponding":false},{"id":78835,"name":"Ariel Alejandro Bazzini","orcid":"0000-0002-2251-5174","position":5,"is_corresponding":false},{"id":644168,"name":"Luciana Andrea Castellano","orcid":"0000-0002-3250-6116","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:18.414003Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}