{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T19:02:29Z","timestamp":1774897349959,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v13112331","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T03:12:56Z","timestamp":1638328376000},"page":"2331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing"],"prefix":"10.3390","volume":"13","author":[{"given":"Jun","family":"Yang","sequence":"first","affiliation":[{"name":"Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Hao","sequence":"additional","affiliation":[{"name":"Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Virus Isolation and Serology Laboratory, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad T.","family":"Rehman","sequence":"additional","affiliation":[{"name":"Virus Isolation and Serology Laboratory, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helene C.","family":"Highbarger","sequence":"additional","affiliation":[{"name":"Virus Isolation and Serology Laboratory, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suranjana","family":"Goswami","sequence":"additional","affiliation":[{"name":"Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brad T.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine A.","family":"Rehm","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin L.","family":"Dewar","sequence":"additional","affiliation":[{"name":"Virus Isolation and Serology Laboratory, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-2763","authenticated-orcid":false,"given":"Weizhong","family":"Chang","sequence":"additional","affiliation":[{"name":"Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1474-1796","authenticated-orcid":false,"given":"Tomozumi","family":"Imamichi","sequence":"additional","affiliation":[{"name":"Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory, Frederick, MD 21702, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ref_1","unstructured":"Coffin, J.M., Hughes, S.H., and Varmus, H.E. 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