Isolation of an active Lv1 gene from cattle indicates that tripartite motif protein-mediated innate immunity to retroviral infection is widespread among mammals.
Lv1/TRIM5alpha (tripartite motif 5alpha) has recently emerged as an important factor influencing species-specific permissivity to retroviral infection in a range of primates, including humans. Old World monkey TRIM5alpha blocks human immunodeficiency virus type 1 (HIV-1) infectivity, and the human and New World monkey TRIM5alpha 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 TRIM5alpha ortholog uncertain, and we therefore refer to it as bovine Lv1. Bovine Lv1 is closely related to primate TRIM5alpha 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.
Ylinen
Laura M J
LM
Department of Infection, Royal Free and University College Medical School, University College London, 46 Cleveland Street, London W1T4JF, United Kingdom.
Keckesova
Zuzana
Z
Webb
Benjamin L J
BL
Gifford
Robert J M
RJ
Smith
Timothy P L
TP
Towers
Greg J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D044966:Anti-Retroviral Agents / Q000302:isolation & purification / Q000378:metabolism*; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000302:isolation & purification; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007668:Kidney / Q000166:cytology; D008969:Molecular Sequence Data; D051078:Platyrrhini; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012190:Retroviridae / Q000502:physiology*; D012192:Retroviridae Infections / Q000276:immunology / Q000517:prevention & control*; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D044966:Anti-Retroviral Agents; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D004279:DNA, Viral; D011506:Proteins; D034741:RNA, Small Interfering; D012367:RNA, Viral; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases