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

Elizabeth A. Dietrich, Greg Brennan, Betsy Ferguson, Roger W. Wiseman, David O'Connor, Shiu Lok Hu

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)9956-9963
    Number of pages8
    JournalJournal of Virology
    Volume85
    Issue number19
    DOIs
    StatePublished - Oct 2011

    Fingerprint

    Macaca fascicularis
    functional diversity
    Macaca
    Human immunodeficiency virus 2
    Feline Immunodeficiency Virus
    Feline immunodeficiency virus
    HIV-2
    Philippines
    Human immunodeficiency virus 1
    HIV-1
    Acquired Immunodeficiency Syndrome
    Mauritius
    Alleles
    Cyclophilin A
    genetic polymorphism
    Indochina
    cyclophilins
    alleles
    Macaca nemestrina
    Indonesia

    ASJC Scopus subject areas

    • Immunology
    • Virology

    Cite this

    Variable prevalence and functional diversity of the antiretroviral restriction factor TRIMCyp in Macaca fascicularis. / Dietrich, Elizabeth A.; Brennan, Greg; Ferguson, Betsy; Wiseman, Roger W.; O'Connor, David; Hu, Shiu Lok.

    In: Journal of Virology, Vol. 85, No. 19, 10.2011, p. 9956-9963.

    Research output: Contribution to journalArticle

    Dietrich, Elizabeth A. ; Brennan, Greg ; Ferguson, Betsy ; Wiseman, Roger W. ; O'Connor, David ; Hu, Shiu Lok. / Variable prevalence and functional diversity of the antiretroviral restriction factor TRIMCyp in Macaca fascicularis. In: Journal of Virology. 2011 ; Vol. 85, No. 19. pp. 9956-9963.
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