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HIV-1C env and gag Variation in the Cerebrospinal Fluid and Plasma of Patients with HIV-Associated Cryptococcal Meningitis in Botswana
Authors:Nametso Kelentse  Sikhulile Moyo  Mompati L. Mogwele  Doreen Ditshwanelo  Baitshepi Mokaleng  Natasha O. Moraka  Kwana Lechiile  Tshepo B. Leeme  David S. Lawrence  Rosemary Musonda  Ishmael Kasvosve  Thomas S. Harrison  Joseph N. Jarvis  Simani Gaseitsiwe
Abstract:HIV-1 compartmentalization in reservoir sites remains a barrier to complete HIV eradication. It is unclear whether there is variation in HIV-1 env and gag between cerebrospinal fluid (CSF) and plasma of individuals with HIV-associated cryptococcal meningitis (CM). We compared HIV-1 env characteristics and the gag cytotoxic T-lymphocyte (CTL) escape mutations from CSF and plasma samples. Employing population-based Sanger sequencing, we sequenced HIV-1 env from CSF of 25 patients and plasma of 26 patients. For gag, 15 CSF and 21 plasma samples were successfully sequenced. Of these, 18 and 9 were paired env and gag CSF/plasma samples, respectively. There was no statistically significant difference in the proportion of CCR5-using strains in the CSF and plasma, (p = 0.50). Discordant CSF/plasma virus co-receptor use was found in 2/18 pairs (11.1%). The polymorphisms in the HIV-1 V3 loop were concordant between the two compartments. From the HIV-1 gag sequences, three pairs had discordant CTL escape mutations in three different epitopes of the nine analyzed. These findings suggest little variation in the HIV-1 env between plasma and CSF and that the CCR5-using strains predominate in both compartments. HIV-1 gag CTL escape mutations also displayed little variation in CSF and plasma suggesting similar CTL selective pressure.
Keywords:Botswana   CCR5   CXCR4   cerebrospinal fluid   co-receptor   cryptococcal meningitis   escape mutations   human immunodeficiency virus (HIV)   plasma
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