Human immunodeficiency virus type 1 subtype C exhibits higher transactivation activity of tat than subtypes B and E

Although human immunodeficiency virus type 1 (HIV-1) subtypes C and E are expanding faster and seem to be of greater global significance than HIV-1 subtype B, there is only little information about Tat activity of such non-B subtypes. Here, we showed evidence that subtype C Tat exhibits higher transcriptional activity from the HIV-1 long-terminal repeat (LTR) in a human T-cell line, compared with subtypes B and E. This higher activity of subtype C Tat was not due to the LTR, but to the Tat sequence variability. We examined three candidate regions with sequence for the higher activity of subtype C Tat, such as the cysteine-rich motif, the basic domain, and the 2nd exon. The results showed that the variation in subtype C Tat at two amino acid residues, Ser⁵⁷ and Glu⁶³ in stead of Arg⁵⁷ and Gln⁶³ in subtypes B and E, within and close to the basic domain were involved in the higher activity of subtype C Tat. This variation did not affect its nuclear localization activity. Thus, there may be a significant advantage for the high Tat activity on subtype C replication.