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Updated: Jul 19, 2026

Nucleocapsid Annealing-Mediated Electrophoresis (NAME) Assay Allows the Rapid Identification of HIV-1 Nucleocapsid Inhibitors
Published on: January 19, 2015
Trim5alpha accelerates degradation of cytosolic capsid associated with productive HIV-1 entry
Udayan Chatterji1, Michael D Bobardt, Peter Gaskill
1Departments of Immunology, Molecular and Integrative Neurosciences, and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Abstract:
The TRIM5alpha (tripartite motif 5alpha protein) has been linked to the cross-species restriction in human immunodeficiency virus type 1 (HIV-1) infection of non-human cells, but the mechanism by which this occurs remains to be fully elucidated. Here we demonstrate that the capsid (CA) protein of HIV-1 is more rapidly degraded in cells expressing monkey TRIM5alpha than in cells expressing human TRIM5alpha. Other proteins encoded by Gag and Pol are not subject to TRIM5alpha-mediated accelerated degradation. The accelerated CA degradation by TRIM5alpha apparently occurs via a nonproteosomal pathway. TRIM5alpha selectively accelerates degradation of the CA population, which reached the cytosol of restrictive cells, but not the CA population, which ended into the vesicular compartment. Given that cytosolic CA represents "productively" entered cores, whereas vesicular CA represents "nonproductively" entered cores, our findings suggest that TRIM5alpha interrupts the infectious pathway of HIV-1 by acting on the incoming cytosolic CA. The mode of viral entry does not influence the accelerated degradation of cytosolic CA by TRIM5alpha. Thus, this study reveals a correlation between TRIM5alpha-mediated HIV-1 restriction and a selective degradation of cytosolic CA normally associated with productive viral entry.
Insights
Monkey TRIM5alpha rapidly degrades HIV-1 capsid protein, interrupting viral entry. This selective degradation of cytosolic capsid protein explains TRIM5alpha
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- The tripartite motif 5alpha (TRIM5alpha) protein restricts human immunodeficiency virus type 1 (HIV-1) infection across species.
- The precise mechanism of TRIM5alpha-mediated restriction, particularly its effect on viral components, requires further elucidation.
Purpose of the Study:
- To investigate the mechanism by which TRIM5alpha restricts HIV-1 infection.
- To determine the specific viral components targeted by TRIM5alpha during the restriction process.
Main Methods:
- Compared the degradation rates of HIV-1 proteins in cells expressing either human or monkey TRIM5alpha.
- Investigated the cellular localization (cytosolic vs. vesicular) of targeted viral proteins.
- Assessed the impact of TRIM5alpha on viral entry pathways.
Main Results:
- Monkey TRIM5alpha significantly accelerated the degradation of HIV-1 capsid (CA) protein compared to human TRIM5alpha.
- Other HIV-1 Gag and Pol proteins were not subject to TRIM5alpha-mediated accelerated degradation.
- TRIM5alpha selectively targeted cytosolic CA, associated with productive viral entry, via a non-proteasomal pathway.
Conclusions:
- TRIM5alpha restricts HIV-1 by selectively degrading cytosolic capsid protein, a critical step in productive viral entry.
- This selective degradation mechanism effectively interrupts the HIV-1 infectious pathway, independent of the viral entry mode.
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