{"doi":"10.1128/jvi.76.22.11254-11264.2002","title":"Roles of Nonstructural Protein nsP2 and Alpha/Beta Interferons in Determining the Outcome of Sindbis Virus Infection","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>Alphaviruses productively infect a variety of vertebrate and insect cell lines. In vertebrate cells, Sindbis virus redirects cellular processes to meet the needs of virus propagation. At the same time, cells respond to virus replication by downregulating virus growth and preventing dissemination of the infection. The balance between these two mechanisms determines the outcome of infection at the cellular and organismal levels. In this report, we demonstrate that a viral nonstructural protein, nsP2, is a significant regulator of Sindbis virus-host cell interactions. This protein not only is a component of the replicative enzyme complex required for replication and transcription of viral RNAs but also plays a role in suppressing the antiviral response in Sindbis virus-infected cells. nsP2 most likely acts by decreasing interferon (IFN) production and minimizing virus visibility. Infection of murine cells with Sindbis virus expressing a mutant nsP2 leads to higher levels of IFN secretion and the activation of 170 cellular genes that are induced by IFN and/or virus replication. Secreted IFN protects naive cells against Sindbis virus infection and also stops viral replication in productively infected cells. Mutations in nsP2 can also attenuate Sindbis virus cytopathogenicity. Such mutants can persist in mammalian cells with defects in the alpha/beta IFN (IFN-α/β) system or when IFN activity is neutralized by anti-IFN-α/β antibodies. These findings provide new insight into the alphavirus-host cell interaction and have implications for the development of improved alphavirus expression systems with better antigen-presenting potential.</jats:p>","journal":"Journal of Virology","year":2002,"id":17775,"datarank":8.45740429415538,"base_score":5.488937726156687,"endowment":5.488937726156687,"self_citation_contribution":0.8233406589235032,"citation_network_contribution":7.634063635231876,"self_endowment_contribution":0.8233406589235032,"citer_contribution":7.634063635231876,"corpus_percentile":null,"corpus_rank":null,"citation_count":241,"citer_count":190,"citers_with_citation_signal":164,"citers_with_endowment":164,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":125973,"name":"Rafik Z. 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Frolova","orcid":"0000-0001-6523-9336","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.488937726156687,"endowment":5.488937726156687,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12388685","pmcid":"PMC136776","openalex_id":"https://openalex.org/W2136628013","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R37 AI024134","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS018596","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"T32 AI007417","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI24134","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"NS18596","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS038932","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"T32AI07417","title":null}],"total_grants":7,"fwci":3.5846,"citation_percentile":0.93157699,"influential_citations":16,"citation_trend":[{"year":2012,"count":14},{"year":2013,"count":17},{"year":2014,"count":6},{"year":2015,"count":6},{"year":2016,"count":12},{"year":2017,"count":9},{"year":2018,"count":8},{"year":2019,"count":14},{"year":2020,"count":7},{"year":2021,"count":7},{"year":2022,"count":9},{"year":2023,"count":13},{"year":2024,"count":10},{"year":2025,"count":11},{"year":2026,"count":4}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/136776","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc136776?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/136776","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.76.22.11254-11264.2002","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.76.22.11254-11264.2002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12388685","host_type":"repository"}],"fields_of_study":["Viral Infections and Outbreaks Research","Viral Infections and Vectors","interferon and immune responses","Biology","Medicine","Alphavirus Infections","Animals","Cell Line","Cricetinae","Cysteine Endopeptidases","Interferon-alpha","Interferon-beta","Mice","Mutation","Oligonucleotide Array Sequence Analysis","RNA, Viral","Sindbis Virus","Transcription, Genetic","Viral Proteins","Virulence","Virus Replication"],"mesh_terms":["Animals","Cell Line","Cysteine Endopeptidases","Cricetinae","Mutation","RNA, Viral","Sindbis Virus","Transcription, Genetic","Viral Proteins","Virulence","Virus Replication","Interferon-alpha","Interferon-beta","Alphavirus Infections","Oligonucleotide Array Sequence Analysis","Mice"],"keywords":["Sindbis virus","Biology","Alphavirus","Virology","Viral replication","Virus","Alphavirus infection","Interferon","Cell culture","RNA","Gene","Genetics"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.24864087.v1","title":"Additional file 1 of GETV nsP2 plays a critical role in the interferon antagonism and viral pathogenesis","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.24864087","title":"Additional file 1 of GETV nsP2 plays a critical role in the interferon antagonism and viral pathogenesis","publisher":"figshare","resource_type":"Dataset"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-02T23:17:41.322984Z","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":[]}