Amino acid substitutions at the HIV-1 transframe region significantly impair virus infectivity

Abstract

A transframe region within HIV-1 Gag-Pol (referred to as p6* or p6pol), directly linked to the protease (PR) N-terminus, plays a pivotal role in modulating PR activation. To identify specific p6* residues involved in PR activation, we created a series of p6* mutants by making substitutions for conserved p6* residues. Our results indicate that some p6* mutants were defective in terms of virus infectivity, despite displaying a wild-type virus particle processing pattern. Mutations at p6* F8 reduced virus infectivity associated with insufficient virus processing, due in part to impaired PR maturation and RT packaging. Our data strongly suggest that conserved Phe (F) residues at position 8 of p6* are involved in the PR maturation process.

The HIV-1 Gag Protein Displays Extensive Functional and Structural Roles in Virus Replication and Infectivity

“…Interestingly, Yu et al [ 111 ] demonstrated that point mutations at highly conserved residues, specifically at position F8 in the transframe p6 region of Gag–Pol, result in insufficient viral processing due to impaired protease and reverse transcriptase activity.…”