IQGAP1 Negatively Regulates HIV-1 Gag Trafficking and Virion Production

• Published in: Cell reports (Cambridge) Vol. 30; no. 12; pp. 4065 - 4081.e4
• Main Authors: Sabo, Yosef, de los Santos, Kenia, Goff, Stephen P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.03.2020; Elsevier
• Subjects: Amino Acid Sequence; Cell Membrane - metabolism; gag Gene Products, Human Immunodeficiency Virus - chemistry; gag Gene Products, Human Immunodeficiency Virus - metabolism; HEK293 Cells; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - metabolism; HIV-1 Gag trafficking; HIV-1 virion formation; Humans; IQGAP1 inhibition of HIV-1; IQGAP1-Gag interaction; Nucleocapsid - metabolism; Protein Binding; Protein Domains; Protein Transport; ras GTPase-Activating Proteins - metabolism; Virion - metabolism; IQGAP1-Gag interaction; HIV-1 virion formation; IQGAP1 inhibition of HIV-1; HIV-1 Gag trafficking
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.03.002

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. [Display omitted] •Depletion of IQGAP1 increases HIV-1 viral particle release•Overexpression of IQGAP1 reduces HIV-1 viral particle release•IQGAP1 interacts with the NC and p6 domains of the HIV-1 Gag protein•IQGAP1 negatively regulates HIV-1 Gag accumulation at the plasma membrane IQGAP1 is a ubiquitously expressed master regulator of many cellular processes, including intracellular trafficking. Sabo et al. demonstrate that in a variety of cell types, IQGAP1 acts as a negative regulator of HIV-1 viral particle release by reducing accumulation of the Gag viral structural protein at the plasma membrane.