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

Area of Science:

• Virology
• Molecular Biology
• Structural Biology

Background:

• The matrix (MA) domain of HIV-1 Gag is crucial for membrane binding during viral replication.
• The precise impact of altered Gag membrane binding early in the post-infection phase remains unclear.

Purpose of the Study:

• To investigate how MA mutations affecting Gag membrane binding influence the characteristics of newly produced HIV-1 particles.
• To elucidate the role of MA in early post-entry events and functional core formation.

Main Methods:

• Characterization of two MA mutants (V6R and L20K) using virological, biochemical, and morphological analyses.
• Assessment of Gag processing, core morphogenesis, core uncoating, reverse transcription, and viral DNA integration.

Main Results:

• The V6R mutation (decreased membrane binding) altered Gag processing, core morphogenesis, impaired core uncoating, reverse transcription, and DNA integration.
• The L20K mutation (increased membrane binding) primarily reduced integrated DNA levels, leaving viral components and morphology largely unaffected.

Conclusions:

• HIV-1 MA plays a significant role in establishing a functional viral core.
• MA is critical for multiple post-entry steps in the HIV-1 replication cycle, including viral DNA formation and integration.