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.
