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Variable prevalence and functional diversity of the antiretroviral restriction factor TRIMCyp in Macaca fascicularis

Elizabeth A Dietrich1, Greg Brennan, Betsy Ferguson

  • 1Department of Microbiology, University of Washington, Seattle, WA 98121, USA.

Journal of Virology
|July 29, 2011
PubMed

Insights

The TRIMCyp restriction factor in macaques shows diverse prevalence and function, impacting AIDS research models. This study analyzes TRIMCyp in Macaca fascicularis, revealing varied distribution and restriction specificities against retroviruses like HIV.

Area of Science:

  • Immunology
  • Genetics
  • Virology

Background:

  • The TRIM5 gene encodes the TRIMCyp retroviral restriction factor, inhibiting postentry replication.
  • TRIMCyp is found in several Asian macaque species, with Macaca fascicularis frequently used in AIDS research.
  • Detailed analysis of TRIMCyp in Macaca fascicularis has been limited.

Purpose of the Study:

  • To investigate the prevalence of TRIMCyp in Macaca fascicularis populations from Indonesia, Indochina, the Philippines, and Mauritius.
  • To characterize the retroviral restriction specificity of TRIMCyp alleles in Macaca fascicularis.
  • To identify genetic variations influencing TRIMCyp function and expression.

Main Methods:

  • Prevalence analysis of TRIMCyp in macaque samples from diverse geographic locations.
  • Functional analysis of TRIMCyp restriction specificity against HIV-1, HIV-2, and FIV.
  • Mutagenesis studies to pinpoint amino acid residues critical for restriction specificity and expression.

Main Results:

  • TRIMCyp is more frequent in Indonesian than Indochinese Macaca fascicularis and present in Philippine samples, but absent in Mauritian macaques.
  • Identified TRIMCyp alleles with distinct specificities, restricting HIV-2/FIV or HIV-1/FIV, but not HIV-1 or HIV-2 respectively.
  • Polymorphisms in the cyclophilin A (CypA) domain (residues 369/446) determine restriction specificity, while coiled-coil domain variations affect expression/stability.

Conclusions:

  • Macaca fascicularis exhibits the most diverse TRIM5 restriction factors documented in any primate species.
  • TRIMCyp variations in Macaca fascicularis have significant implications for understanding retroviral evolution.
  • These findings are crucial for refining the use of Macaca fascicularis as a model in AIDS research.

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