Mild cognitive impairment in a clinically latent HIV-1 patient population
Journal of virus eradication
Designing an ideal vaccine against HIV-1 has been difficult due to enormous genetic variability as a result of high replication rate and lack of proof reading activity of reverse transcriptase leading to emergence of genetic variants and recombinants. Genetic studies reveal that HIV-1 Nef gene shows extensive genetic diversity. Functional studies have been carried out mostly with Nef derived from subtype B pNL4-3 virus. The rationale of this study was to characterize genetic variations that are
... variations that are present in the nef gene from HIV-1 infected individuals from North-India and determine their functional implications. Methods: Genomic DNA was isolated from PBMCs of HIV-1 infected patients and nef gene was PCR amplified with specific primers followed by cloning, sequencing and sequence analyses using bioinformatics tools for predicting HIV-1 subtypes, recombination events and conservation of domains. The unique representative variants were then characterized with respect to their ability to downregulate CD4 and MHC-1 expressed on cell surface. Results: Phylogenetic analysis of nef variants revealed sequence similarity with consensus subtype B and B/C recombinants. Bootscan analysis of some of our variants showed homology to B/C recombinant and some to wild type nef B. High amino acid variations was observed among our most of the variants. dN/dS ratio revealed 80% purifying selection and 20% diversifying selection implying the importance of variable mutations of Nef variants. There were some variants that possessed mutations in the functional domains of Nef responsible for its CD4 and MHC-1 activity. Conclusions: We observed enhanced biological activities in some of our variants may be the result of amino acid substitutions in their functional domains. In summary, the CD4 and MHC-1 downregulation activity of Nef must be used by virus to its maximum advantage.