Protein Tat, HIV2 (Tat)

HIV-1 (Human immunodeficiency virus type 1) and HIV-2 Tat proteins increase the level of transcription from their corresponding LTRs (long terminal repeats). The HIV-1 and HIV-2 LTRs contain an element called TAR (transactivation responsive RNA element) that extends downstream from the transcription initiation site and is critical for Tat activation. Tat recognizes TAR and recruits the cyclin T1-CDK9 complex (P-TEFb complex), which in turn hyperphosphorylates the RNA polymerase II for efficient elongation. The CDK9 component of P-TEFb and other TAT-activated kinases hyperphosphorylate the C-terminal of RNA Pol II that becomes stabilized.. Extracellular circulating Tat can be endocytosed by surrounding uninfected cells by binding to several surface receptors. Low endosomal pH allows Tat to cross the endosomal membrane into the cytosol and eventually further translocate to the nucleus, thereby inducing severe cellular dysfunction from cell activation to cell death.