{"doi":"10.1093/pnasnexus/pgae102","title":"Cryogenic electron microscopy and tomography reveal imperfect icosahedral symmetry in alphaviruses","abstract":"Alphaviruses are spherical, enveloped RNA viruses with two-layered icosahedral architecture. The structures of many alphaviruses have been studied using cryogenic electron microscopy (cryo-EM) reconstructions, which impose icosahedral symmetry on the viral particles. Using cryogenic electron tomography (cryo-ET), we revealed a polarized symmetry defect in the icosahedral lattice of Chikungunya virus (CHIKV) in situ, similar to the late budding particles, suggesting the inherent imperfect symmetry originates from the final pinch-off of assembled virions. We further demonstrated this imperfect symmetry is also present in in vitro purified CHIKV and Mayaro virus, another arthritogenic alphavirus. We employed a subparticle-based single-particle analysis protocol to circumvent the icosahedral imperfection and boosted the resolution of the structure of the CHIKV to ∼3 Å resolution, which revealed detailed molecular interactions between glycoprotein E1-E2 heterodimers in the transmembrane region and multiple lipid-like pocket factors located in a highly conserved hydrophobic pocket. This complementary use of in situ cryo-ET and single-particle cryo-EM approaches provides a more precise structural description of near-icosahedral viruses and valuable insights to guide the development of structure-based antiviral therapies against alphaviruses.","journal":"PNAS Nexus","year":2024,"id":425398,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1223051,"name":"Guan-Chin Su","orcid":"0000-0003-3251-5511","position":1,"is_corresponding":false},{"id":387969,"name":"Jason T. Kaelber","orcid":"0000-0001-9426-1030","position":2,"is_corresponding":false},{"id":228227,"name":"Grigore Pintilie","orcid":"0000-0002-0848-5335","position":3,"is_corresponding":false},{"id":561591,"name":"Muyuan Chen","orcid":"0000-0003-1311-7868","position":4,"is_corresponding":false},{"id":399446,"name":"Jing Jin","orcid":"0000-0003-3994-8600","position":5,"is_corresponding":false},{"id":440343,"name":"Albert J. Auguste","orcid":"0000-0001-9048-0041","position":6,"is_corresponding":false},{"id":91649,"name":"Wah Chiu","orcid":"0000-0002-8910-3078","position":7,"is_corresponding":false},{"id":399445,"name":"David Chmielewski","orcid":"0000-0002-4498-7949","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:58:26.927596Z","pmid":"38525304","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":[]}