Krystal Colón1, Fabián Vázquez-Santiago2, Vanessa Rivera-Amill2, Gisela Delgado3, Steven E Massey3, Valerie Wojna4, Richard J Noel5, Loyda M Meléndez1. 1. Department of Microbiology and Medical Zoology, University of Puerto Rico Medical Sciences Campus, San Juan, PR. 2. Department of Basic Sciences, Microbiology Division, Ponce Health Sciences University-School of Medicine, Ponce Research Institute, Ponce PR. 3. Department of Biology, Río Piedras Campus, San Juan, PR. 4. Specialized NeuroAIDS Program, University of Puerto Rico-Medical Sciences Campus, San Juan, PR, 00936, USA; Department of Internal Medicine, Neurology Division, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936, USA. 5. Department of Basic Sciences, Biochemistry Division, Ponce Health Sciences University-School of Medicine, Ponce Research Institute, Ponce PR.
Abstract
OBJECTIVE: HIV-1 variants with different tropisms are associated with various neuropathologies. This study intends to determine if this correlation is determined by unique viral env sequences. We hypothesize that HIV-1 envelope gene sequence changes are associated with cognition status. METHODS: Viral RNA was extracted from peripheral blood mononuclear cells (PBMCs) co-cultures derived from HIV-1 infected Hispanic women that had been characterized for HIV associated neurocognitive disorders (HAND). RESULTS: Analyses of the C2V4 region of HIV gp120 demonstrated that increased sequence diversity correlates with cognition status as sequences derived from subjects with normal cognition exhibited less diversity than sequences derived from subjects with cognitive impairment. In addition, differences in V3 and V4 loop charges were also noted as well as differences in the N-glycosylation of the V4 region. CONCLUSIONS: Our data suggest that the genetic signature within the C2V4 region may contribute to the pathogenesis of HAND. HIV env sequence characteristics for the isolates grouped in milder forms of HAND can provide insightful information of prognostic value to assess neurocognitive status in HIV+ subjects, particularly during the era of highly prevalent milder forms of HAND.
OBJECTIVE:HIV-1 variants with different tropisms are associated with various neuropathologies. This study intends to determine if this correlation is determined by unique viral env sequences. We hypothesize that HIV-1envelope gene sequence changes are associated with cognition status. METHODS: Viral RNA was extracted from peripheral blood mononuclear cells (PBMCs) co-cultures derived from HIV-1 infected Hispanicwomen that had been characterized for HIV associated neurocognitive disorders (HAND). RESULTS: Analyses of the C2V4 region of HIV gp120 demonstrated that increased sequence diversity correlates with cognition status as sequences derived from subjects with normal cognition exhibited less diversity than sequences derived from subjects with cognitive impairment. In addition, differences in V3 and V4 loop charges were also noted as well as differences in the N-glycosylation of the V4 region. CONCLUSIONS: Our data suggest that the genetic signature within the C2V4 region may contribute to the pathogenesis of HAND. HIV env sequence characteristics for the isolates grouped in milder forms of HAND can provide insightful information of prognostic value to assess neurocognitive status in HIV+ subjects, particularly during the era of highly prevalent milder forms of HAND.
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