Seattle Children's Hospital Research Institute Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on February 19, 2008, 10.1073/pnas.0709258105

This Article
Right arrow Full Text (PDF)
Right arrow Supporting Information
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Virgen, C. A.
Right arrow Articles by Hatziioannou, T.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Virgen, C. A.
Right arrow Articles by Hatziioannou, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

MICROBIOLOGY
Independent genesis of chimeric TRIM5-cyclophilin proteins in two primate species

Cesar A. Virgen*, Zerina Kratovac*, Paul D. Bieniasz*,{dagger},{ddagger}, and Theodora Hatziioannou*,{ddagger}

*Aaron Diamond AIDS Research Center and {dagger}Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016

Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved December 12, 2007 (received for review September 28, 2007)

Abstract

The host range of retroviruses is influenced by antiviral proteins such as TRIM5, a restriction factor that recognizes and inactivates incoming retroviral capsids. Remarkably, in Owl monkeys (omk), a cyclophilin A (CypA) cDNA has been transposed into the TRIM5 locus, resulting in the expression of a TRIM5-CypA fusion protein (TRIMCyp) that restricts retroviral infection based on the retroviral capsid-binding specificity of CypA. Here, we report that the seemingly improbable genesis of TRIMCyp has, in fact, occurred twice, and pigtailed macaques (pgt) express an independently generated TRIMCyp protein. The omkTRIMCyp and pgtTRIMCyp proteins restrict infection by several lentiviruses, but their specificities are distinguishable. Surprisingly, pgtTRIMCyp cannot bind to or restrict HIV-1 capsids as a consequence of a point mutation close to the Cyp:capsid-binding interface that was acquired during or after transposition of pgtCypA. However, the same mutation confers on pgtTRIMCyp the ability to restrict FIV in the presence of cyclosporin A, a drug that normally abolishes the interaction between pgtTRIMCyp or omkTRIMCyp and lentiviral capsids. Overall, an intuitively unlikely evolutionary event has, in fact, occurred at least twice in primates and represents a striking example of convergent evolution in divergent species.

HIV-1 | LINE | restriction factor

Footnotes

Author contributions: C.A.V., P.D.B., and T.H. designed research; C.A.V., Z.K., and T.H. performed research; C.A.V., Z.K., P.D.B., and T.H. analyzed data; and P.D.B. and T.H. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

{ddagger}To whom correspondence may be addressed. E-mail: pbienias{at}adarc.org or thatziio{at}adarc.org

© 2008 by The National Academy of Sciences of the USA


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


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