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.

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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