IQGAP1 Negatively Regulates HIV-1 Gag Trafficking and Virion Production
| Autor: | Stephen P. Goff, Kenia de los Santos, Yosef Sabo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell type viruses HIV Infections Endocytosis gag Gene Products Human Immunodeficiency Virus General Biochemistry Genetics and Molecular Biology Virus Article 03 medical and health sciences 0302 clinical medicine IQGAP1 Protein Domains Hiv 1 gag Humans Amino Acid Sequence Nucleocapsid lcsh:QH301-705.5 Budding Chemistry Cell Membrane Virion Intracellular vesicle Cell biology Protein Transport 030104 developmental biology HEK293 Cells lcsh:Biology (General) ras GTPase-Activating Proteins HIV-1 030217 neurology & neurosurgery Function (biology) Protein Binding |
| Zdroj: | Cell Reports, Vol 30, Iss 12, Pp 4065-4081.e4 (2020) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. Graphical Abstract In Brief 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. |
| Databáze: | OpenAIRE |
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