HIV Tat protein: Is Tat-C much trickier than Tat-B?

Out of various subtypes of human immunodeficiency virus type 1 (HIV-1), subtype B and C cause most of the infections worldwide. Clade specific differences have been reported in differences in clinical picture of HIV pathogenesis. Transcription of the HIV-1 genome is regulated by the interaction of HIV Tat protein to the trans-activation response (TAR) element. The differential binding of clade B and C Tat proteins to TAR and differences in activation of NF-κB cascade leading to differential transactivation capacity and cytokine expression has been examined in this study. More stable Tat-TAR complex formation by Tat-C revealed by EMSA and higher TNF-α expression shown by Tat-C compared to Tat-B leads to higher NF-κB activation, which may be plausible cause for higher transactivation by Tat-C as obtained by FACS analysis. This comparative study would be helpful in understanding the basic mechanism of clade specific Tat protein differences and their functional relationships.