The role of Tat in HIV-1 replication: an activator and/or a suppressor?

Tat is a key trans-activator of HIV-1 gene transcription and major progress has been accomplished in recent years in regard to understanding its mechanism of action. An important breakthrough was the identification of the TAR-Tat-Cyclin (Cyc) T1-Cyclin-dependent kinase 9 (CDK9) complex, in which CDK9 can hyperphosphorylate the carboxyl-terminus domain (CTD) of the RNA polymerase (RNAP) II complex. A different activity of Tat has recently been identified in reverse transcription. Notably, mutated HIV-1 that lacks a functional Tat protein cannot efficiently generate reverse transcription products following infection of permissive cells. Furthermore, Tat can also inhibit reverse transcriptase activity in cell-free assays and can act as a suppressor of reverse transcription at late stages in the viral life cycle. This suppressor activity of Tat can restrict the premature reverse transcription of viral RNA in the cytoplasm and allows the viral genome to be packaged as intact RNA molecules.