{"doi":"10.1128/mbio.00431-22","title":"Emergence of Compensatory Mutations Reveals the Importance of Electrostatic Interactions between HIV-1 Integrase and Genomic RNA","abstract":"In addition to its catalytic function, HIV-1 integrase (IN) binds to the viral RNA genome (gRNA) through positively charged residues (i.e., R262, R263, R269, K273) within its C-terminal domain (CTD) and regulates proper virion maturation. Mutation of these residues results in the formation of morphologically aberrant viruses blocked at an early reverse transcription stage in cells. Here we show that compensatory substitutions in nearby negatively charged aspartic acid residues (i.e., D256N, D270N) restore the ability of IN to bind gRNA for these mutant viruses and result in the formation of accurately matured infectious virions. Similarly, individual charge reversal substitutions at D256 as well as other nearby positions (i.e., D278, D279) are all sufficient to enable the respective IN mutants to bind gRNA, and subsequently restore reverse transcription and virion infectivity. Taken together, our findings reveal the importance of highly pliable electrostatic interactions in IN-gRNA binding.","journal":"mBio","year":2022,"id":261201,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"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":823436,"name":"Tung Dinh","orcid":"0000-0002-5141-3281","position":1,"is_corresponding":false},{"id":823437,"name":"Abhishek Kumar","orcid":"0000-0001-5880-8123","position":2,"is_corresponding":false},{"id":629337,"name":"Kasyap Tenneti","orcid":null,"position":3,"is_corresponding":false},{"id":324217,"name":"Jenna E. Eschbach","orcid":"0000-0001-9107-4504","position":4,"is_corresponding":false},{"id":562269,"name":"Keanu Davis","orcid":"0000-0002-4256-9911","position":5,"is_corresponding":false},{"id":372397,"name":"Robert J. Gifford","orcid":"0000-0003-4028-9884","position":6,"is_corresponding":false},{"id":324221,"name":"Mamuka Kvaratskhelia","orcid":"0000-0003-3800-0033","position":7,"is_corresponding":false},{"id":324222,"name":"Sebla B. Kutluay","orcid":"0000-0001-5549-7032","position":8,"is_corresponding":false},{"id":334924,"name":"Christian Shema Mugisha","orcid":"0000-0002-0517-7986","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T00:26:12.158801Z","pmid":"35975921","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":[]}