4.8 Article

TRIMCyp expression in old world primates Macaca nemestrina and Macaca fascicularis

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0709511105

Keywords

convergent evolution; cyclophilin A; HIV; retroviruses; TRIM5 alpha

Funding

  1. NCRR NIH HHS [P51 RR00016] Funding Source: Medline
  2. NIAID NIH HHS [K08 AI067138, K08 AI061738] Funding Source: Medline

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Primates have evolved a variety of restriction factors that prevent retroviral replication. One such factor, TRIM5 alpha, mediates a postentry restriction in many Old World primates. Among New World primates, Aotus trivirgatus exerts a similar early restriction mediated by TRIMCyp, a TRIMS-cyclophilin A (CypA) chimera resulting from a CypA retrotransposition between exons 7 and 8 of the TRIM5 gene. Macaca nemestrina do not express TRIM5 alpha; therefore, we asked whether these animals and related Old World primates express TRIMCyp. RT-PCR of total RNA from M. nemestrina and Macaca fascicularis yielded three TRIMCyp amplification products, one of which is predicted to encode a TRIMCyp chimera containing a full-length CypA. Unlike A. trivirgatus, genomic sequencing of M. nemestrina and M. fascicularis identifies a CypA retrotransposition in the 3' untranslated region of the TRIMS locus. There is approximate to 78% homology between the predicted protein sequences of Old World and New World primate TRIMCyp, with most of the differences found in the TRIMS-derived sequence. Notably, exon 7 is absent from both M. nemestrina and M. fascicularis TRIMCyp. Neither M. nemestrina nor M. fascicularis TRIMCyp could restrict HIV-1 or simian immunodeficiency virus SIVmac in an in vitro infectivity assay. The discovery of TRIMCyp in both M. nemestrina and M. fascicularis indicates that TRIMCyp expression may be more common among Old World primates than previously believed. Convergent evolution of TRIMCyp in both Old World and New World primates suggests that TRIMCyp may have provided evolutionary advantages.

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