{"doi":"10.3390/v13112331","title":"A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing","abstract":"We have recently reported that a recombinant HIV-1NL4.3 containing Met-to-Ile change at codon 50 of integrase (IN) (IN:M50I) exhibits suppression of the virus release below 0.5% of WT HIV, and the released viral particles are replication-incompetent due to defects in Gag/GagPol processing by inhibition of the initiation of autoprocessing of GagPol polyproteins in the virions and leads to replication-incompetent viruses. The coexisting Ser-to-Asn change at codon 17 of IN or Asn-to-Ser mutation at codon 79 of RNaseH (RH) compensated the defective IN:M50I phenotype, suggesting that both IN and RH regulate an HIV infectability. In the current study, to elucidate a distribution of the three mutations during anti-retroviral therapy among patients, we performed a population analysis using 529 plasma virus RNA sequences obtained through the MiSeq. The result demonstrated that 14 plasma HIVs contained IN:M50I without the compensatory mutations. Comparing the sequences of the 14 viruses with that of the defective virus illustrated that only Val-to-Ile change at codon 151 of IN (IN:V151I) existed in the recombinant virus. This IN:V151I is known as a polymorphic mutation and was derived from HIVNL4.3 backbone. A back-mutation at 151 from Ile-to-Val in the defective virus recovered HIV replication capability, and Western Blotting assay displayed that the back-mutation restored Gag/GagPol processing in viral particles. These results demonstrate that a combination of IN:M50I and IN:V151I mutations, but not IN:M50I alone, produces a defective virus.","journal":"Viruses","year":2021,"id":207099,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":687974,"name":"Ming Hao","orcid":"0000-0001-7618-1934","position":1,"is_corresponding":false},{"id":75369,"name":"Muhammad Attique Khan","orcid":"0000-0002-6347-4890","position":2,"is_corresponding":false},{"id":792639,"name":"M. Tauseef Rehman","orcid":null,"position":3,"is_corresponding":false},{"id":521714,"name":"Helene C. Highbarger","orcid":null,"position":4,"is_corresponding":false},{"id":585812,"name":"Qian Chen","orcid":"0000-0002-2768-6570","position":5,"is_corresponding":false},{"id":519255,"name":"Suranjana Goswami","orcid":"0000-0003-2677-7523","position":6,"is_corresponding":false},{"id":60621,"name":"Brad T. Sherman","orcid":"0000-0001-5815-7359","position":7,"is_corresponding":false},{"id":427793,"name":"Catherine Rehm","orcid":"0000-0003-2049-5824","position":8,"is_corresponding":false},{"id":432708,"name":"Robin Dewar","orcid":"0000-0002-7840-3155","position":9,"is_corresponding":false},{"id":421689,"name":"Weizhong Chang","orcid":"0000-0002-1413-2763","position":10,"is_corresponding":false},{"id":421688,"name":"Tomozumi Imamichi","orcid":"0000-0002-1474-1796","position":11,"is_corresponding":false},{"id":519258,"name":"Jun Yang","orcid":"0000-0003-2775-8914","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:51:45.688025Z","pmid":"34835137","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":[]}