The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1 retroviral restriction factor activities.
The rhesus macaque tripartite motif containing protein TRIM5alpha specifically restricts HIV-1 infection at an early post-entry step before reverse transcription [Stremlau, M., Owens, C. M., Perron, M. J., Kiessling, M., Autissier, P. & Sodroski, J. (2004) Nature 427, 848-853]. Here, we show that the human and African green monkey (AGM) TRIM5alpha genes encode Ref1 and Lv1 antiretroviral activities, respectively. Expression of TRIM5alpha in permissive cat cells renders them resistant to restriction-sensitive murine leukemia virus but not closely related insensitive virus. Disruption of TRIM5alpha expression in human and AGM cells with small interfering RNA rescues infectivity of restricted virus without affecting unrestricted virus. We also demonstrate that the activity of the murine restriction factor Fv1 depends on TRIM5alpha expression when Fv1 is expressed in human cells. Furthermore, a drug that modifies the behavior of the related promyelocytic leukemia protein PML specifically rescues infection by viruses restricted by human TRIM5alpha. Alignment of the TRIM5alpha proteins from rhesus macaque and AGM indicates an 18-aa insertion. We speculate that this insertion may contribute to the broader specificity of the AGM TRIM5alpha restriction as compared with the human and rhesus macaque proteins.
Keckesova
Zuzana
Z
Wohl Virion Center, Division of Infection and Immunity, University College London, London W1T 4JF, United Kingdom.
Ylinen
Laura M J
LM
Towers
Greg J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000235:genetics / Q000378:metabolism*; D000090103:Antiviral Restriction Factors; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D002522:Chlorocebus aethiops / Q000235:genetics*; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010087:Oxides / Q000378:metabolism; D011815:R Factors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000378:metabolism*; D012192:Retroviridae Infections / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000998:Antiviral Agents; D000090103:Antiviral Restriction Factors; D001152:Arsenicals; D002352:Carrier Proteins; D006131:Growth Inhibitors; D010087:Oxides; D034741:RNA, Small Interfering; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D000077237:Arsenic Trioxide