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Journal of Virology, November 2007, p. 11713-11721, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01468-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

An Active TRIM5 Protein in Rabbits Indicates a Common Antiviral Ancestor for Mammalian TRIM5 Proteins{triangledown}

Torsten Schaller, Stéphane Hué, and Greg J. Towers*

MRC Centre for Medical Molecular Virology, Department of Infection, Royal Free and University College Medical School, UCL, London W1T4JF, United Kingdom

Received 5 July 2007/ Accepted 18 August 2007

The recent identification of antiretroviral tripartite motif-bearing restriction factors that protect against retroviral infection has revealed a novel branch of innate immunity. The factors target the retroviral capsid and inhibit infectivity soon after the capsid has entered the cytoplasm by an incompletely characterized mechanism. Restriction is species specific. For example, TRIM5{alpha} from Old World monkeys, but not humans, restricts human immunodeficiency virus type 1 infection. Here, we identify an antiviral TRIM5 molecule in rabbits that is closely related to antiviral TRIM5 of both primates and cattle. We demonstrate that the rabbit TRIM5 protein is active against divergent retroviruses and leads to a strong block to viral DNA synthesis and infectivity. Furthermore, we show that antiviral activity is directed against the viral capsid and that human TRIM5 proteins are dominant negative to restriction in rabbit cells. We propose that the sequence and restriction characteristics conserved between restriction factors from primates, cattle, and rabbits indicate that these factors have evolved from a common ancestor with antiretroviral properties.

* Corresponding author. Mailing address: Windeyer Building, UCL, 46 Cleveland Street, London W1T4JF, United Kingdom. Phone: 44-20 7679 9535. Fax: 44-20 7679 9545. E-mail: g.towers{at}ucl.ac.uk

{triangledown} Published ahead of print on 29 August 2007.

Journal of Virology, November 2007, p. 11713-11721, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01468-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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