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

Authors

• Laura M.J. Ylinen, Royal Free and University College Medical School, UCL, London W1T4JF, United Kingdom
• Zuzana Keckesova, Royal Free and University College Medical School, UCL, London W1T4JF, United Kingdom
• Benjamin L.J. Webb, Royal Free and University College Medical School, UCL, London W1T4JF, United Kingdom
• Robert J.M. Gifford, Royal Free and University College Medical School, UCL, London W1T4JF, United Kingdom
• Timothy P.L. Smith, USDA-ARSFollow
• Greg J. Towers, Royal Free and University College Medical School, UCL, London W1T4JF, United Kingdom

Document Type

Article

Date of this Version

August 2006

Comments

Published in JOURNAL OF VIROLOGY, Aug. 2006, p. 7332–7338.

Abstract

Lv1/TRIM5α (tripartite motif 5α) has recently emerged as an important factor influencing species-specific permissivity to retroviral infection in a range of primates, including humans. Old World monkey TRIM5α blocks human immunodeficiency virus type 1 (HIV-1) infectivity, and the human and New World monkey TRIM5α 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 TRIM5α ortholog uncertain, and we therefore refer to it as bovine Lv1. Bovine Lv1 is closely related to primate TRIM5α 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.