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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

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 (tripartite motif 5) 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 blocks human immunodeficiency virus type 1 (HIV-1) infectivity, and the human and New World monkey TRIM5 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 ortholog uncertain, and we therefore refer to it as bovine Lv1. Bovine Lv1 is closely related to primate TRIM5 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.

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