Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation

Abstract

HIV transactivator protein (Tat) plays a pivotal role in viral replication through modulation of cellular transcription factors and transactivation of viral genomic transcription. The effect of HIV-1 Tat on reverse transcription has long been described in the literature, however, that of HIV-2 is understudied. Sequence homology between Tat proteins of HIV-1 and 2 is estimated to be less than 30%, and the main difference lies within their N-terminal region. Here, we describe Y44A-inactivating mutation of HIV-2 Tat, studying its effect on capsid production, reverse transcription, and the efficiency of proviral transcription. Investigation of the mutation was performed using sequence- and structure-based in silico analysis and in vitro experiments. Our results indicate that the Y44A mutant HIV-2 Tat inhibited the activity and expression of RT (reverse transcriptase), in addition to diminishing Tat-dependent LTR (long terminal repeat) transactivation. These findings highlight the functional importance of the acidic domain of HIV-2 Tat in the regulation of reverse transcription and transactivation of the integrated provirions.