{"doi":"10.3390/v14122606","title":"Host-Dependent Modifications of Packaged Alphavirus Genomic RNA Influence Virus Replication in Mammalian Cells","abstract":"Alphaviruses must interact efficiently with two distinct host environments in order to replicate and transmit between vertebrate and mosquito hosts. Some host-origin-dependent differences in virus particle composition that appear to facilitate the transmission cycle are known. However, the impact of host-mediated modification of packaged viral genomic RNA on subsequent infection has not been previously investigated. Here we show that in human (HEK-293) cells, mosquito-derived Sindbis virus (SINV) replicates and spreads faster, producing a more infectious virus than its mammalian-derived counterpart. This enhanced replication is neither a result of differences in the stability nor the production of the infecting genomic RNA. Nevertheless, purified genomic RNA from mosquito-derived SINV established infection in HEK-293 cells more efficiently than that of mammalian-derived SINV, indicating that the genomic RNA itself is different between the two producing hosts and this difference is a determinant of infection. In agreement with this idea, we show that mosquito-derived SINV genomic RNA is a more active template for translation than mammalian-derived SINV genomic RNA, and we attribute this difference to host-dependent changes in modification of packaged genomic RNA as determined by LC/MS-MS. Our data support the hypothesis that among other factors, the host-dependent modification profile of the packaged vRNA is likely to play an important role in the efficiency of SINV infection and replication in mammalian cells.","journal":"Viruses","year":2022,"id":285732,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":250686,"name":"Liewei L. Yan","orcid":"0000-0002-3692-0621","position":1,"is_corresponding":false},{"id":250687,"name":"Hani Zaher","orcid":"0000-0002-7424-3617","position":2,"is_corresponding":false},{"id":356670,"name":"Richard W. Hardy","orcid":"0000-0001-6912-6291","position":3,"is_corresponding":false},{"id":744684,"name":"John M. Crawford","orcid":"0000-0002-6209-5258","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T00:29:44.944555Z","pmid":"36560610","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":[]}