Association of viral and host genetic architecture with the status of neurocognitive disorder in HIV-infected individuals.

Abstract

The polymorphisms in host genes like CCR5, CCR2, SDF, and MBL as well as the viral nef gene have been shown to influence HIV infection followed by the development of HIV-associated neurocognitive disorder (HAND). In this preliminary study with a limited number of samples, we have tried to associate the genetic polymorphism from the host and viral genetic factors with the neurocognitive status along with immuno-virological parameters. The total RNA was isolated from ten unlinked plasma samples containing five samples from each group with and without HAND based on IHDS (International HIV dementia scale) Score < 9.5 &> 9.5 respectively. The CCR5, CCR2, SDF, MBL, and HIV nef genes were amplified and digested with restriction enzymes except for the nef gene amplicon. The digested products of host genes were analyzed by Restriction Fragment Length Polymorphism (RFLP) to understand the presence of allelic variants whereas the sequencing analysis of HIV nef amplicons. CCR5 delta 32 heterozygous variants were present in two samples from the HAND group. Three samples with HAND showed SDF-1 3' heterozygous allelic variant while the MBL-2gene presented with a homozygous mutant allele (D/D) in codon 52, heterozygous mutant allele (A/B) in codon 54, and codon 57 (A/C) for all samples except IHDS-2irrespective of dementia status. Furthermore, amino acid alignment of Nef sequences confirmed the heterogeneity while prediction of the HLA binding epitopes further explored its effect on functional motifs with variable binding efficiency like, epitopes GAFDLSFFL (aa 83) and LTFGWCFKL (aa 138) are binding with HLA molecules at 60% and 80% respectively. Thus, host genetics evidently influence predisposition to HIV infection and HAND. The genetic variability in the nef gene from both groups resulted in altering the functionality of specific domains and showing its impact on the progression of the disease which needs to be explored.