{"doi":"10.1128/jvi.07223-11","title":"Early Events in Alphavirus Replication Determine the Outcome of Infection","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>\n                    Alphaviruses are a group of important human and animal pathogens. They efficiently replicate to high titers\n                    <jats:italic>in vivo</jats:italic>\n                    and in many commonly used cell lines of vertebrate origin. They have also evolved effective means of interfering with development of the innate immune response. Nevertheless, most of the alphaviruses are known to induce a type I interferon (IFN) response\n                    <jats:italic>in vivo</jats:italic>\n                    . The results of this study demonstrate that the first hours postinfection play a critical role in infection spread and development of the antiviral response. During this window, a balance is struck between virus replication and spread in vertebrate cells and IFN response development. The most important findings are as follows: (i) within the first 2 to 4 h postinfection, alphavirus-infected cells become unable to respond to IFN-β, and this occurs before the virus-induced decrease in STAT1 phosphorylation in response to IFN treatment. (ii) Most importantly, very low, subprotective doses of IFN-β, which do not induce the antiviral response in uninfected cells, have a very strong stimulatory effect on the cells' ability to express type I IFN and activate interferon-stimulated genes during subsequent infection with Sindbis virus (SINV). (iii) Small changes in SINV nsP2 protein affect its ability to inhibit cellular transcription and IFN release. Thus, the balance between type I IFN induction and the ability of the virus to develop further rounds of infection is determined in the first few hours of virus replication, when only low numbers of cells and infectious virus are involved.\n                  </jats:p>","journal":"Journal of Virology","year":2012,"id":17839,"datarank":2.0242619998757285,"base_score":4.02535169073515,"endowment":4.02535169073515,"self_citation_contribution":0.6038027536102726,"citation_network_contribution":1.420459246265456,"self_endowment_contribution":0.6038027536102726,"citer_contribution":1.420459246265456,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":48,"citers_with_citation_signal":42,"citers_with_endowment":42,"datacite_reuse_total":0,"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":126182,"name":"Maryna Akhrymuk","orcid":null,"position":1,"is_corresponding":false},{"id":126183,"name":"Ivan Akhrymuk","orcid":null,"position":2,"is_corresponding":false},{"id":125572,"name":"Svetlana Atasheva","orcid":null,"position":3,"is_corresponding":false},{"id":125411,"name":"Elena I. Frolova","orcid":"0000-0001-6523-9336","position":4,"is_corresponding":false},{"id":124134,"name":"Ilya Frolov","orcid":"0000-0002-8548-2517","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.02535169073515,"endowment":4.02535169073515,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22345447","pmcid":"PMC3347369","openalex_id":"https://openalex.org/W2151629825","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI070207","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01AI073301","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R56AI091705","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI070207","title":null}],"total_grants":4,"fwci":1.7963,"citation_percentile":0.84702241,"influential_citations":2,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":5},{"year":2014,"count":1},{"year":2015,"count":6},{"year":2016,"count":6},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":3},{"year":2020,"count":4},{"year":2021,"count":6},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2024,"count":4},{"year":2025,"count":4},{"year":2026,"count":2}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://jvi.asm.org/content/jvi/86/9/5055.full.pdf","host_type":"journal"},{"url":"https://jvi.asm.org/content/jvi/86/9/5055.full.pdf","host_type":"BRONZE"},{"url":"https://jvi.asm.org/content/jvi/86/9/5055.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.07223-11","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.07223-11","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22345447","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.662.8637","host_type":""},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3347369","host_type":"repository"}],"fields_of_study":["interferon and immune responses","Immune Response and Inflammation","Viral Infections and Vectors","Medicine","Biology","Alphavirus","Animals","Cricetinae","Cysteine Endopeptidases","Down-Regulation","Gene Expression Regulation, Viral","Interferon Type I","Mice","Models, Biological","Mutation","Phosphorylation","STAT1 Transcription Factor","Transcription, Genetic","Virus Replication"],"mesh_terms":["Alphavirus","Animals","Cysteine Endopeptidases","Cricetinae","Interferon Type I","Models, Biological","Mutation","Phosphorylation","Transcription, Genetic","Virus Replication","Down-Regulation","Gene Expression Regulation, Viral","STAT1 Transcription Factor","Mice"],"keywords":["Biology","Alphavirus","Sindbis virus","Interferon","Virology","Virus","Viral replication","Alphavirus infection","STAT1","Immune system","Innate immune system","Interferon type I","Immunology","Gene","RNA","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-03T01:35:54.563756Z","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":[]}