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Published online on February 19, 2008, 10.1073/pnas.0709511105
PNAS | March 4, 2008 | vol. 105 | no. 9 | 3569-3574


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From the Cover
BIOLOGICAL SCIENCES / MICROBIOLOGY
TRIMCyp expression in Old World primates Macaca nemestrina and Macaca fascicularis

Greg Brennan{dagger}, Yury Kozyrev{ddagger}, and Shiu-Lok Hu{dagger},{ddagger},§

Departments of {dagger}Microbiology and {ddagger}Pharmaceutics, and §Washington National Primate Research Center, University of Washington, Seattle, WA 98121

Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved January 10, 2008 (received for review October 5, 2007)

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 TRIM5–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 TRIM5 locus. There is {approx}78% homology between the predicted protein sequences of Old World and New World primate TRIMCyp, with most of the differences found in the TRIM5-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.

convergent evolution | cyclophilin A | HIV | retroviruses | TRIM5{alpha}


Author contributions: G.B., Y.K., and S.-L.H. designed research; G.B. and Y.K. performed research; G.B., Y.K., and S.-L.H. analyzed data; and G.B. and S.-L.H. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. EU371628EU371639 and EU371641).

See Commentary on page 3177.

To whom correspondence should be addressed at: University of Washington, 3000 Western Avenue, Seattle, WA 98121. E-mail: hus{at}bart.rprc.washington.edu

© 2008 by The National Academy of Sciences of the USA


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Related Commentary in PNAS:

Chance favors a prepared genome
Jonathan P. Stoye and Melvyn W. Yap
PNAS 2008 105: 3177-3178. [Extract] [Full Text]  



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J. P. Stoye and M. W. Yap
Chance favors a prepared genome
PNAS, March 4, 2008; 105(9): 3177 - 3178.
[Full Text] [PDF]