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We investigated the relationship between HIV-1 subtype C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment-naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function. We identified a tyrosine at position 45 (45Y) as a signature for neurocognitive impairment and histidine (45H) as a signature in the non-impaired individuals. The presence of signature 45Y was associated by 3.66 times higher GDS, 525 times higher plasma viral load, 15.84 times higher proviral load, and 60% lower absolute CD4-T cell count compared with those without the signature. Additionally, we identified four conserved Vpr fragment sequences, PEDQGPQREPYNEWTLE (5\u201321), LGQYIY (42\u201347), TYGDTW (49\u201354), and PEDQGPQREPYNEW (5\u201318), that were associated with higher plasma viral load and proviral load. The implication of these findings is that variation of Vpr leads to neurocognitive impairment in HIV infection and worsens the progression of disease in general by promoting the production of provirus, promoting HIV replication and depletion of CD4+ T cells in the periphery.<\/jats:p>","DOI":"10.1089\/aid.2022.0022","type":"journal-article","created":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T00:48:46Z","timestamp":1668818926000},"page":"166-175","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["HIV-1 Subtype C Vpr Amino Acid Residue 45Y and Specific Conserved Fragments Are Associated with Neurocognitive Impairment and Markers of Viral Load"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0586-7212","authenticated-orcid":false,"given":"Vurayai","family":"Ruhanya","sequence":"first","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa."},{"name":"Department of Medical Microbiology, University of Zimbabwe, Harare, Zimbabwe."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme Brendon","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H.","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Psychology and Behavioral Neuroscience, University of Missouri-St Louis, University Boulevard, St Louis, Missouri, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Joska","sequence":"additional","affiliation":[{"name":"MRC Unit of Anxiety and Stress Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soraya","family":"Seedat","sequence":"additional","affiliation":[{"name":"MRC Unit of Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Nyandoro","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Zimbabwe, Harare, Zimbabwe."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard Helmuth","family":"Glashoff","sequence":"additional","affiliation":[{"name":"Division of Medical Microbiology, Stellenbosch University, Cape Town, South Africa."},{"name":"National Health Laboratory Service (NHLS), Tygerberg Business Unity, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1318-5994","authenticated-orcid":false,"given":"Susan","family":"Engelbrecht","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"e_1_3_5_2_2","first-page":"11","article-title":"Identification of HIV-1 vpr product and function","volume":"3","author":"Cohen EA","year":"1990","unstructured":"Cohen EA, , Terwilliger EF, , Jalinoos Y, et al. 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