HIV-1 matrix mutations that alter gag membrane binding modulate mature core formation and post-entry events
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Updated: Jan 25, 2026

Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle GUV Membranes
Published on: July 28, 2016
Yuta Hikichi1, Eri Takeda2, Masayuki Fujino3
1AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan; The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
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).
Insights
Altering the matrix (MA) domain of HIV-1 Gag affects virus replication. Mutations impairing Gag membrane binding disrupt core formation and viral DNA steps, while increased binding mainly reduces DNA integration.
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.
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