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Variable Prevalence and Functional Diversity of the Antiretroviral Restriction Factor TRIMCyp in Macaca fascicularis

The retroviral restriction factor TRIMCyp, derived from the TRIM5 gene, blocks replication at a postentry step. TRIMCyp has so far been found in four species of Asian macaques, Macaca fascicularis, M. mulatta, M. nemestrina, and M. leonina. M. fascicularis is commonly used as a model for AIDS resear... Full description

Journal Title: Journal of Virology 2011, Vol. 85(19), p.9956
Main Author: Dietrich, Elizabeth A.
Other Authors: Brennan, Greg , Ferguson, Betsy , Wiseman, Roger W. , O'Connor, David , Hu, Shiu-Lok
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1098-5514 ; PMID: 21795330
Link: http://jvi.asm.org/content/85/19/9956.full
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recordid: asm21795330
title: Variable Prevalence and Functional Diversity of the Antiretroviral Restriction Factor TRIMCyp in Macaca fascicularis
format: Article
creator:
  • Dietrich, Elizabeth A.
  • Brennan, Greg
  • Ferguson, Betsy
  • Wiseman, Roger W.
  • O'Connor, David
  • Hu, Shiu-Lok
subjects:
  • Antiviral Agents -- Metabolism
  • Lentiviruses, Primate -- Immunology
  • Macaca Fascicularis -- Genetics
  • Proteins -- Genetics
ispartof: Journal of Virology, 2011, Vol. 85(19), p.9956
description: The retroviral restriction factor TRIMCyp, derived from the TRIM5 gene, blocks replication at a postentry step. TRIMCyp has so far been found in four species of Asian macaques, Macaca fascicularis, M. mulatta, M. nemestrina, and M. leonina. M. fascicularis is commonly used as a model for AIDS research, but TRIMCyp has not been analyzed in detail in this species. We analyzed the prevalence of TRIMCyp in samples from Indonesia, Indochina, the Philippines, and Mauritius. We found that TRIMCyp is present at a higher frequency in Indonesian than in Indochinese M. fascicularis macaques and is also present in samples from the Philippines. TRIMCyp is absent in Mauritian M. fascicularis macaques. We then analyzed the restriction specificity of TRIMCyp derived from three animals of Indonesian origin. One allele, like the prototypic TRIMCyp alleles described for M. mulatta and M. nemestrina, restricts human immunodeficiency virus type 2 (HIV-2) and feline immunodeficiency virus (FIV) but not HIV-1. The others restrict HIV-1 and FIV but not HIV-2. Mutagenesis studies confirmed that polymorphisms at amino acid residues 369 and 446 in TRIMCyp (or residues 66 and 143 in the cyclophilin A [CypA] domain) confer restriction specificity. Additionally, we identified a polymorphism in the coiled-coil domain that appears to affect TRIMCyp expression or stability. Taken together, these data show that M. fascicularis has the most diverse array of TRIM5 restriction factors described for any primate species to date. These findings are relevant to our understanding of the evolution of retroviral restriction factors and the use of M. fascicularis models in AIDS research.
language: eng
source:
identifier: ISSN: 1098-5514 ; PMID: 21795330
fulltext: fulltext
issn:
  • 1098-5514
  • 10985514
url: Link


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titleVariable Prevalence and Functional Diversity of the Antiretroviral Restriction Factor TRIMCyp in Macaca fascicularis
creatorDietrich, Elizabeth A. ; Brennan, Greg ; Ferguson, Betsy ; Wiseman, Roger W. ; O'Connor, David ; Hu, Shiu-Lok
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descriptionThe retroviral restriction factor TRIMCyp, derived from the TRIM5 gene, blocks replication at a postentry step. TRIMCyp has so far been found in four species of Asian macaques, Macaca fascicularis, M. mulatta, M. nemestrina, and M. leonina. M. fascicularis is commonly used as a model for AIDS research, but TRIMCyp has not been analyzed in detail in this species. We analyzed the prevalence of TRIMCyp in samples from Indonesia, Indochina, the Philippines, and Mauritius. We found that TRIMCyp is present at a higher frequency in Indonesian than in Indochinese M. fascicularis macaques and is also present in samples from the Philippines. TRIMCyp is absent in Mauritian M. fascicularis macaques. We then analyzed the restriction specificity of TRIMCyp derived from three animals of Indonesian origin. One allele, like the prototypic TRIMCyp alleles described for M. mulatta and M. nemestrina, restricts human immunodeficiency virus type 2 (HIV-2) and feline immunodeficiency virus (FIV) but not HIV-1. The others restrict HIV-1 and FIV but not HIV-2. Mutagenesis studies confirmed that polymorphisms at amino acid residues 369 and 446 in TRIMCyp (or residues 66 and 143 in the cyclophilin A [CypA] domain) confer restriction specificity. Additionally, we identified a polymorphism in the coiled-coil domain that appears to affect TRIMCyp expression or stability. Taken together, these data show that M. fascicularis has the most diverse array of TRIM5 restriction factors described for any primate species to date. These findings are relevant to our understanding of the evolution of retroviral restriction factors and the use of M. fascicularis models in AIDS research.
subjectAntiviral Agents -- Metabolism ; Lentiviruses, Primate -- Immunology ; Macaca Fascicularis -- Genetics ; Proteins -- Genetics;
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