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Multiple interactions between the ESCRT machinery and arrestin-related proteins: implications for PPXY-dependent
Susanne Rauch1, Juan Martin-Serrano
1Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom.
Journal of Virology
|December 31, 2010
Summary
Arrestin-related trafficking (ART) proteins act as adaptors in viral budding by connecting HECT ubiquitin ligases to the ESCRT pathway. These ART proteins facilitate viral egress and ESCRT-III recruitment, offering new insights into virus-host interactions.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Enveloped viruses utilize late domains for efficient release from host cells.
- Late domains interact with the endosomal sorting complex required for transport (ESCRT) machinery for viral egress.
- PPXY late domains engage HECT ubiquitin ligases, but the ESCRT-III recruitment mechanism is unclear.
Purpose of the Study:
- To investigate the role of arrestin-related trafficking (ART) proteins as adaptors in PPXY-dependent viral budding.
- To elucidate the mechanism of ESCRT-III recruitment mediated by HECT ubiquitin ligases and ART proteins.
Main Methods:
- Co-immunoprecipitation assays to assess protein interactions.
- Overexpression studies to evaluate the impact on viral budding.
- Analysis of ubiquitination status of ART proteins.
Main Results:
- ART proteins interact with HECT ubiquitin ligases (WWP1, WWP2, Itch) and ESCRT components (ALIX, Tsg101).
- ARTs are recruited to viral budding sites, and their overexpression inhibits murine leukemia virus (MLV) budding in a PPXY-dependent manner.
- WWP1 alters the ubiquitination status of ARRDC1, suggesting a role in ubiquitination-dependent budding.
Conclusions:
- ART proteins function as crucial adaptors in PPXY-mediated viral budding.
- ARTs provide alternative pathways for ESCRT-III recruitment by bridging HECT ubiquitin ligases and the ESCRT machinery.
- This study reveals a novel mechanism for viral egress involving ART proteins and ubiquitination.
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