{"doi":"10.1128/jvi.02680-15","title":"The SD1 Subdomain of Venezuelan Equine Encephalitis Virus Capsid Protein Plays a Critical Role in Nucleocapsid and Particle Assembly","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>Venezuelan equine encephalitis virus (VEEV) is an important human and animal pathogen, for which no safe and efficient vaccines or therapeutic means have been developed. Viral particle assembly and budding processes represent potential targets for therapeutic intervention. However, our understanding of the mechanistic process of VEEV assembly, RNA encapsidation, and the roles of different capsid-specific domains in these events remain to be described. The results of this new study demonstrate that the very amino-terminal VEEV capsid-specific subdomain SD1 is a critical player in the particle assembly process. It functions in a virus-specific mode, and its deletion, mutation, or replacement by the same subdomain derived from other alphaviruses has strong negative effects on infectious virus release. VEEV variants with mutated SD1 accumulate adaptive mutations in both SD1 and SD2, which result in a more efficiently replicating phenotype. Moreover, efficient nucleocapsid and particle assembly proceeds only when the two subdomains, SD1 and SD2, are derived from the same alphavirus. These two subdomains together appear to form the central core of VEEV nucleocapsids, and their interaction is one of the driving forces of virion assembly and budding. The similar domain structures of alphavirus capsid proteins suggest that this new knowledge can be applied to other alphaviruses.</jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE</jats:bold>\n            Alphaviruses are a group of human and animal pathogens which cause periodic outbreaks of highly debilitating diseases. Despite significant progress made in understanding the overall structure of alphavirus and VEEV virions, and glycoprotein spikes in particular, the mechanistic process of nucleocapsid assembly, RNA encapsidation, and the roles of different capsid-specific domains in these processes remain to be described. Our new data demonstrate that the very amino-terminal subdomain of Venezuelan equine encephalitis virus capsid protein, SD1, plays a critical role in the nucleocapsid assembly. It functions synergistically with the following SD2 (helix I) and appears to form a core in the center of nucleocapsid. The core formation is one of the driving forces of alphavirus particle assembly.\n          </jats:p>","journal":"Journal of Virology","year":2016,"id":17608,"datarank":0.3731428258228695,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.10437890543866121,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.10437890543866121,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":5,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":121993,"name":"Valeria Lulla","orcid":"0000-0002-6605-0727","position":1,"is_corresponding":false},{"id":125442,"name":"Dal Young Kim","orcid":null,"position":2,"is_corresponding":false},{"id":125411,"name":"Elena I. Frolova","orcid":"0000-0001-6523-9336","position":3,"is_corresponding":false},{"id":124134,"name":"Ilya Frolov","orcid":"0000-0002-8548-2517","position":4,"is_corresponding":false},{"id":125441,"name":"Josephine M. Reynaud","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26656680","pmcid":"PMC4733989","openalex_id":"https://openalex.org/W2195567157","authors":[],"funders":[{"funder_name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","grant_id":"AI070207","title":null},{"funder_name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","grant_id":"AI095449","title":null},{"funder_name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","grant_id":"AI073301","title":null},{"funder_name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","grant_id":"AI118867","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI070207","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI073301","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI095449","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI118867","title":null}],"total_grants":8,"fwci":1.0212,"citation_percentile":0.81471606,"influential_citations":1,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":2},{"year":2021,"count":1},{"year":2023,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://jvi.asm.org/content/jvi/90/4/2008.full.pdf","host_type":"journal"},{"url":"https://doi.org/10.1128/jvi.02680-15","host_type":"GREEN"},{"url":"https://jvi.asm.org/content/jvi/90/4/2008.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02680-15","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26656680","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4733989","host_type":"repository"},{"url":"https://researchonline.lshtm.ac.uk/id/eprint/2534201/","host_type":"repository"}],"fields_of_study":["Mosquito-borne diseases and control","Viral Infections and Outbreaks Research","vaccines and immunoinformatics approaches","Biology","Medicine","Amino Acid Sequence","Animals","Capsid Proteins","Cell Line","Cricetinae","DNA Mutational Analysis","Encephalitis Virus, Venezuelan Equine","Microscopy, Electron, Transmission","Molecular Sequence Data","Nucleocapsid","Protein Structure, Tertiary","Viral Plaque Assay","Virion","Virus Assembly"],"mesh_terms":["Amino Acid Sequence","Animals","Cell Line","DNA Mutational Analysis","Encephalitis Virus, Venezuelan Equine","Cricetinae","Molecular Sequence Data","Viral Plaque Assay","Virion","Protein Structure, Tertiary","Virus Assembly","Nucleocapsid","Capsid Proteins","Microscopy, Electron, Transmission"],"keywords":["Alphavirus","Venezuelan equine encephalitis virus","Capsid","Biology","Virology","Togaviridae","RNA","Virus","Mutant","Genetics","Gene"],"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":"2026-06-02T19:32:41.030643Z","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":[]}