IQGAP1 Negatively Regulates HIV-1 Gag Trafficking and Virion Production

Cell Rep. 2020 Mar 24;30(12):4065-4081.e4. doi: 10.1016/j.celrep.2020.03.002.

Abstract

IQGAP1 is a master regulator of many cellular processes, including intracellular vesicle trafficking and endocytosis. We show that depletion of IQGAP1 in a variety of cell types increases the release of HIV-1 infectious virions and that overexpression diminishes virion production, with neither affecting the early stages of infection. IQGAP1 negatively regulates the steady-state levels of HIV-1 Gag at the plasma membrane, the site of assembly. We establish that IQGAP1 interacts with both the nucleocapsid and p6 domains of Gag, and interaction with either domain is sufficient for its regulatory function. Finally, we demonstrate that IQGAP1 regulation is independent of HIV-1 Gag "late-domains" sequences required by the virus to recruit the cellular ESCRT machinery. Thus, we provide evidence that IQGAP1 is a negative regulatory factor inhibiting efficient budding of HIV-1 by reducing Gag accumulation at the plasma membrane.

Keywords: HIV-1 Gag trafficking; HIV-1 virion formation; IQGAP1 inhibition of HIV-1; IQGAP1-Gag interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Membrane / metabolism
  • HEK293 Cells
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / metabolism
  • Humans
  • Nucleocapsid / metabolism
  • Protein Binding
  • Protein Domains
  • Protein Transport
  • Virion / metabolism*
  • gag Gene Products, Human Immunodeficiency Virus / chemistry
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • IQ motif containing GTPase activating protein 1
  • gag Gene Products, Human Immunodeficiency Virus
  • ras GTPase-Activating Proteins