HIV-1C env and gag Variation in the Cerebrospinal Fluid and Plasma of Patients with HIV-Associated Cryptococcal Meningitis in Botswana

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.

Partial compartmentalisation of HIV-1 subtype C between lymph nodes, peripheral blood mononuclear cells and plasma

“…The few CTL escape mutations in Gag that differed in frequency between compartments did not coincide with compartmentalisation. Consistent with these results, previous studies have shown that CTL escape is similar between different anatomical locations where the virus is compartmentalised ( Miller et al, 2019 ; Kelentse et al, 2020 ). It is possible that the immune environment is not sufficiently different between the compartments studied to drive significant differences in Gag CTL escape mutations between compartments, and the conserved nature of Gag when compared to Env may also be partly responsible.…”

ViMIC: a database of human disease-related virus mutations, integration sites and cis-effects

“…The immune response plays a key role in the control of virus infection. Several studies have demonstrated that virus mutations allowing escape from the host immune response generally lead to the resistance to antiviral therapy and progression to disease ( 61 , 62 ). For example, in HBV genome, amino acid substitutions in the S region producing the mutated surface antigen may induce immune escape, such as G145R ( 63 ), Q129H ( 64 ) and I195M ( 65 ), etc.…”