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Journal of Virology, August 2006, p. 7332-7338, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00516-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Isolation of an Active Lv1 Gene from Cattle Indicates that Tripartite Motif Protein-Mediated Innate Immunity to Retroviral Infection Is Widespread among Mammals

Laura M. J. Ylinen,1 Zuzana Keckesova,1 Benjamin L. J. Webb,1 Robert J. M. Gifford,1 Timothy P. L. Smith,2 and Greg J. Towers1*

Department of Infection, Royal Free and University College Medical School, UCL, London W1T4JF, United Kingdom,1 USDA-ARS Meat Animal Research Center, Clay Center, Nebraska 689332

Received 13 March 2006/ Accepted 8 May 2006

Lv1/TRIM5{alpha} (tripartite motif 5{alpha}) has recently emerged as an important factor influencing species-specific permissivity to retroviral infection in a range of primates, including humans. Old World monkey TRIM5{alpha} blocks human immunodeficiency virus type 1 (HIV-1) infectivity, and the human and New World monkey TRIM5{alpha} proteins are inactive against HIV-1 but active against divergent murine (N-tropic murine leukemia virus [MLV-N]) and simian (simian immunodeficiency virus from rhesus macaque [SIVmac]) retroviruses, respectively. Here we demonstrate antiviral activity of the first nonprimate TRIM protein, from cattle, active against divergent retroviruses, including HIV-1. The number of closely related human TRIM sequences makes assignment of the bovine sequence as a TRIM5{alpha} ortholog uncertain, and we therefore refer to it as bovine Lv1. Bovine Lv1 is closely related to primate TRIM5{alpha} proteins in the N-terminal RING and B-box 2 domains but significantly less homologous in the C-terminal B30.2 domain, particularly in the region shown to influence antiviral specificity. Intriguingly, some viruses restricted by bovine Lv1, including HIV-1 and MLV-N, are unable to synthesize viral DNA by reverse transcription, whereas restricted HIV-2 makes normal amounts of DNA. The data support the conclusion that TRIM protein-mediated restriction of retroviral infection is a more common attribute of mammals than previously appreciated.

* 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.

Journal of Virology, August 2006, p. 7332-7338, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00516-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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