HIV-1 matrix mutations that alter gag membrane binding modulate mature core formation and post-entry events

Abstract

The matrix (MA) domain of HIV-1 Gag directs membrane binding of the Gag precursor polyprotein during the late events of virus replication. However, the effects of alteration in Gag membrane binding early post-infection are not well understood. To investigate impacts of MA mutations that alter Gag membrane binding on the phenotypes of newly produced virus particles, we extensively characterized two MA mutants by virological, biochemical, and morphological approaches. The V6R mutation, which decreases Gag membrane binding, modified Gag processing and core morphogenesis and impaired core uncoating, reverse transcription, and viral DNA integration. On the other hand, the L20K mutation, which increases Gag membrane binding, primarily decreased integrated DNA levels without affecting the viral components and morphology. These data suggest that HIV-1 MA plays roles in functional core formation and the following post-entry steps of the virus replication cycle. (140/150 words).

Keywords: Core formation; Gag; HIV-1; Integration; Matrix; Membrane binding; Post entry; Reverse transcription; Uncoating.