{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T14:33:13Z","timestamp":1720362793234},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2012\u20103476"],"award-info":[{"award-number":["2012\u20103476"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004348","name":"Stockholm County Council","doi-asserted-by":"publisher","award":["20130042"],"award-info":[{"award-number":["20130042"]}],"id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007165","name":"University of Missouri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:label \/><jats:p>Background: A lower virulence of HIV\u20101 subtype C (HIV\u20101C) is suggested to be related to the global dominance of HIV\u20101C. In this observational study, combining in vivo (clinical monitoring) and in vitro (genotypic, biochemical, and phenotypic assays), we explored whether HIV\u20101C from East Africa (HIV\u20101C<jats:sub>EA<\/jats:sub>) is more pathogenic due to the evolution of a PYxE\u2010insertion (C<jats:sub>PYxEi<\/jats:sub>) in the gag\u2010p6 that also could affect the therapy response. Methods: HIV\u20101B (n\u2009=\u2009112) and HIV\u20101C<jats:sub>EA<\/jats:sub> (n\u2009=\u2009128)\u2010infected individuals residing in Sweden were analyzed with regard to Gag\u2010p6 genotype and clinically monitored. Based on the Gag\u2010p6 characteristics, three HIV\u20101C<jats:sub>EA<\/jats:sub> and one HIV\u20101\u2009B patient\u2010derived p2\u2010INT\u2010recombinant virus (gag\u2010p2\/NCp7\/p1\/p6\/pol\u2010PR\/RT\/IN) were constructed to analyze viral growth kinetics (VGKs) and drug sensitivity assays. Reverse transcriptase (RT) from the same samples was cloned into the heterodimer expression plasmid (pRT6H\u2010PROT) to analyze catalytic efficiency of RT. Results: A higher viral failure rate and lower pre\u2010therapy CD4<jats:sup>+<\/jats:sup> T\u2010cell counts were observed in HIV\u20101C<jats:sub>EA<\/jats:sub>\u2010infected patients compared to HIV\u20101B\u2010infected patients. In Gag\u2010p6, PTAP\u2010duplication was more common in HIV\u20101C. HIV\u20101C<jats:sub>EA<\/jats:sub>\u2010infected patients with signature C<jats:sub>PYxEi,<\/jats:sub> evidenced very low pre\u2010therapy CD4<jats:sup>+<\/jats:sup> T\u2010cell counts and suboptimal gain in CD4<jats:sup>+<\/jats:sup> T\u2010cells following therapy, as compared to the non\u2010C<jats:sub>PYxEi<\/jats:sub>\u2010strains indicating higher virulence. VGKs showed a statistically significant higher replication capacity (RC) for the C<jats:sub>PYxEi<\/jats:sub> viruses than the other two non\u2010C<jats:sub>PYxEi<\/jats:sub> strains. No statistically significant difference was observed in the catalytic efficiency among HIV\u20101C RTs. Conclusions: This is the first evidence of polymerase independent increased virulence and RC in HIV\u20101C<jats:sub>EA<\/jats:sub> following PYxE\u2010insertion that is associated with suboptimal CD4<jats:sup>+<\/jats:sup> T\u2010cell gain following therapy initiation. <jats:bold><jats:italic>J. Med. Virol. 89:106\u2013111, 2017<\/jats:italic><\/jats:bold>. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.24610","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T22:33:18Z","timestamp":1466634798000},"page":"106-111","source":"Crossref","is-referenced-by-count":11,"title":["Increased replication capacity following evolution of PYxE insertion in Gag\u2010p6 is associated with enhanced virulence in HIV\u20101 subtype C from East Africa"],"prefix":"10.1002","volume":"89","author":[{"given":"Shambhu G.","family":"Aralaguppe","sequence":"first","affiliation":[{"name":"Division of Clinical Microbiology Department of Laboratory Medicine Karolinska Institute Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dane","family":"Winner","sequence":"additional","affiliation":[{"name":"University Hospital Translational Laboratory University Hospitals Case Medical Center Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamalendra","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology Christopher Bond Life Sciences Center University of Missouri Columbia Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan G.","family":"Sarafianos","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology Christopher Bond Life Sciences Center University of Missouri Columbia Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel E.","family":"Qui\u00f1ones\u2010Mateu","sequence":"additional","affiliation":[{"name":"University Hospital Translational Laboratory University Hospitals Case Medical Center Cleveland Ohio"},{"name":"Department of Pathology Case Western Reserve University Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"S\u00f6nnerborg","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology Department of Laboratory Medicine Karolinska Institute Stockholm Sweden"},{"name":"Unit of Infectious Diseases Department of Medicine Huddinge Karolinska Institute Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ujjwal","family":"Neogi","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology Department of Laboratory Medicine Karolinska Institute Stockholm 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