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Updated: Dec 25, 2025

Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle GUV Membranes
Published on: July 28, 2016
IQGAP1 Negatively Regulates HIV-1 Gag Trafficking and Virion Production
Yosef Sabo1, Kenia de Los Santos2, Stephen P Goff2
1Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA; Department of Medicine, Division of Infectious Diseases, Columbia University, New York, NY 10032, USA.
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.
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