Intersubtype Genetic Variation of HIV-1 Tat Exon 1

摘要

HIV-1 Tat is a regulatory protein that plays a pivotal role in viral transcription and replication. Our study aimsto investigate the genetic variation of Tat exon 1 in all subtypes of HIV-1: A, B, C, D, F, G, H, J, and K. Weperformed phylogenetic, mutation, and selection pressure analyses on a total of 1,179 sequences of differentsubtypes of HIV-1 Tat obtained from the Los Alamos National Laboratory (LANL). The mean nucleotidedivergences (%) among the analyzed sequences of subtypes A, B, C, D, F, G, H, J, and K were 88, 89, 90, 88,86, 89, 88, 97, and 97, respectively. We revealed that subtype B evolved relatively faster than other subtypes.The second and fifth domains were found comparatively more variable among all subtypes. Site-by-site tests ofpositive selection revealed that several positions in all subtypes were under significant positive selection.Positively selected sites were found in the acidic domain at positions 3, 4, and 19, in the cysteine-rich domainsat positions 24, 29, 32, and 36, in the core domain at position 40, and in the basic domain for the rest of thepositions for all subtypes. Positions 58 and 68 in the basic domain were positively selected in subtypes A, B, Cand B, C, F, respectively. We also observed high variability within positively selected sites in amino acidpositions. Our study findings on HIV-1 Tat genetic variability may contribute to a better understanding of HIV-1evolution as well as to the development of effective Tat-targeted therapeutics and vaccines.