Mild cognitive impairment in a clinically latent HIV-1 patient population

K.N. Devlin, T. Giovannetti, W. Dampier, V. Pirrone, M.R. Nonnemacher, E. Schell, C. Lamberson, J.R. Kurczewski, J.M. Jacobson, D.J. Libon, B. Wigdahl
2015 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
more » ... 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.
doi:10.1016/s2055-6640(20)31379-0 fatcat:4p6cfwgpkvgennml76kjahsiua