Functional significance of HIV-1 tat signature amino acid residues (SAR)

Abstract

Our study is the first of its kind, to our knowledge, to explore the transcriptional differences induced by variant Tat proteins discordant at a single SAR. The findings from the present study would aid in appreciating the functional significance of the S31 residue in subtype C Tat in the context of Endothelial dysfunction. The ability of CS-Tat to induce an activated phenotype in endothelial cells conferring on them enhanced EC migration, invasion and in vitro morphogenesis is of immense significance especially in the context of HIV-associated neuronal and cardiovascular disorders. Since this work explored the angiogenic potential of the variant Tat proteins in isolation as opposed to the context of full-length infectious HIV-1C viruses, it could be considered as a potential limitation of this study. Whether the findings from our study translate to significant differences in disease manifestations in HIV-1, CS vs. CC-Tat subtype-C viral infections, is a question which is still unanswered and beyond the scope of the current study. Additionally, the influence of other viral proteins and their contribution to the differences in the angiogenic responses of variant Tat proteins is an aspect which remains unexplored. The lack of an organized database in India of HIV-associated clinical manifestations is a serious drawback in understanding, devising and executing HIV-1 disease management strategies. The recent studies carried out using more standardized and universally accepted scales of measuring the extent and severity of neurocognitive impairment have suggested a significant proportion of HIV-1 C infected population to be neurocognitively impaired albeit to lesser severity 31–33. In the context of the findings of the present study, the speculations regarding the accuracy and universal applicability of the currently available dementia scales for screening HAND, the prevalence of the less severe forms of HAND being far more common than what was believed previously seems increasingly plausible.