HIV-1C env and gag variation in the cerebrospinal fluid and plasma of patients with HIV-associated cryptococcal meningitis in Botswana

Kelentse, Nametso ; Moyo, Sikhulile ; Mogwele, Mompati L. ; Ditshwanelo, Doreen ; Mokaleng, Baitshepi ; Moraka, Natasha O. ; Lechiile, Kwana ; Leeme, Tshepo B. ; Lawrence, David S. ; Musonda, Rosemary ; Kasvosve, Ishmael ; Harrison, Thomas S. ; Jarvis, Joseph N. ; Gaseitsiwe, Simani (2020-12-07)

CITATION: Kelentse, N. et al. 2020. HIV-1C env and gag variation in the cerebrospinal fluid and plasma of patients with HIV-associated cryptococcal meningitis in Botswana. Viruses, 12(12):1404, doi:10.3390/v12121404.

The original publication is available at https://www.mdpi.com

Article

ENGLISH 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.

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