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Disruption of human TRIM5alpha antiviral activity by nonhuman primate orthologues

Lionel Berthoux1, Sarah Sebastian, David M Sayah

  • 1Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 West 168th St., New York, NY 10032, USA.

Journal of Virology
|May 28, 2005
PubMed

Insights

The TRIM5 protein family influences retroviral infection susceptibility. Heterologous TRIM5 proteins form complexes, altering antiviral activity and virus recognition, particularly impacting murine leukemia virus restriction.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • TRIM5 proteins determine species-specific retroviral infection susceptibility.
  • Human TRIM5alpha (TRIM5alpha(hu)) restricts murine leukemia virus (N-MLV) but has limited effect on HIV-1.
  • Macaque TRIM5alpha (TRIM5alpha(rh)) and owl monkey TRIM5-cyclophilin A (TRIMCyp) restrict HIV-1.

Purpose of the Study:

  • To investigate the functional consequences of TRIM5 orthologue interactions.
  • To determine if TRIM5 proteins from different species can form heteromultimers.
  • To understand how C-terminal domains influence TRIM5 antiviral activity.

Main Methods:

  • Heterologous expression of TRIM5alpha(rh) and TRIMCyp in human cells.
  • Assessing the anti-N-MLV activity of endogenous TRIM5alpha(hu) in the presence of heterologous TRIM5 proteins.
  • Deletion mutagenesis of the cyclophilin domain in TRIMCyp.
  • Analysis of heteromultimerization and colocalization using microscopy.

Main Results:

  • Heterologous expression of TRIM5alpha(rh) or TRIMCyp interfered with endogenous TRIM5alpha(hu)'s anti-N-MLV activity.
  • Deletion of the cyclophilin domain from TRIMCyp abolished interference with TRIM5alpha(hu) activity.
  • TRIM5 orthologues were shown to form heteromultimers and colocalize within cells.
  • The cyclophilin domain is crucial for TRIM5-mediated interference but not for heteromultimerization.

Conclusions:

  • TRIM5 orthologues can form functional heteromultimers.
  • C-terminal domains of TRIM5 proteins modulate the antiviral specificity of these heteromultimers.
  • These findings provide insights into the molecular mechanisms of TRIM5-mediated retroviral restriction.

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