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

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.

Virology
|May 6, 2019
PubMed

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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