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Published on: August 31, 2014
Regulation of CHMP4/ESCRT-III function in human immunodeficiency virus type 1 budding by CC2D1A
Yoshiko Usami1, Sergei Popov, Eric R Weiss
1Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Journal of Virology
|January 20, 2012
Summary
New proteins, CC2D1A and CC2D1B, bind to CHMP4 proteins, regulating human immunodeficiency type 1 (HIV-1) budding. These interactions impact viral release, suggesting novel therapeutic targets for HIV-1 infection.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Human immunodeficiency type 1 (HIV-1) virion detachment relies on ESCRT pathway components, specifically CHMP4 proteins, for viral release.
- CHMP4 proteins are crucial for cleaving viral necks from the cell during budding.
Purpose of the Study:
- To identify and characterize novel proteins interacting with CHMP4 family members.
- To elucidate the role of these interacting proteins in the regulation of HIV-1 budding.
Main Methods:
- Co-immunoprecipitation and protein binding assays to identify CHMP4-interacting proteins.
- Overexpression and small interfering RNA (siRNA) knockdown experiments to assess the impact on HIV-1 budding.
- Analysis of protein domains (DM14) for CHMP4 binding and functional characterization.
Main Results:
- CC2D1A and CC2D1B were identified as high-molecular-weight proteins binding to CHMP4 proteins.
- These interactions, particularly CC2D1A binding to the CHMP4 core, were shown to regulate CHMP4 polymerization and inhibit HIV-1 budding.
- siRNA-mediated knockdown of CC2D1A or CC2D1B modulated HIV-1 budding efficiency.
- The DM14 domains of CC2D1A/B function as novel CHMP4 binding modules, capable of inhibiting HIV-1 budding via CHMP4 sequestration.
- Evidence suggests CC2D1A may also influence HIV-1 budding independently of CHMP4.
Conclusions:
- CC2D1A and CC2D1B are novel regulators of HIV-1 budding through their interaction with CHMP4 proteins.
- The DM14 domains are key CHMP4 binding modules involved in this regulation.
- CC2D1A exhibits potential CHMP4-independent mechanisms affecting viral release, offering multifaceted regulatory roles.
