Identification of amino acid residues in HIV-1 reverse transcriptase that are critical for the proteolytic processing of Gag–Pol precursors

Abstract

The efficient processing of human immunodeficiency virus type 1 Gag–Pol requires not only protease activity but also specific reverse transcriptase (RT) and integrase sequences. However, the critical amino acid residues of the HIV-1 Pol gene involved in protease-mediated Gag–Pol processing have not been precisely defined. Here, we found that the substitution of Thr-128 or Tyr-146 with Ala markedly impaired the proteolytic processing of the MA/CA, p66/p51 and RT/IN sites but did not affect the normal processing of other sites. Moreover, a Thr-128 or Tyr-146 mutation in RT abolished RT dimerization in vitro. These results suggest that Thr-128 and Tyr-146 within the RT region play important roles in protease-mediated Gag–Pol processing. Structured summary of protein interactionsRT and RTphysically interact by cross-linking study (View interaction: 1, 2, 3).CK2 alphaphosphorylatesRT by protein kinase assay (View interaction).