The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1 retroviral restriction factor activities

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 29; pp. 10780 - 10785
• Main Authors: Keckesova, Zuzana, Ylinen, Laura M J, Towers, Greg J
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 20.07.2004
• Subjects: Amino Acid Sequence; Animals; Antiretroviral agents; Antiviral Agents - genetics; Antiviral Agents - metabolism; Arsenic Trioxide; Arsenicals - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cats; Cell Line; Chlorocebus aethiops - genetics; Gene expression; Growth Inhibitors - metabolism; HIV; Human immunodeficiency virus; Human subjects; Humans; Leukemia; Leukemia Virus, Murine - genetics; Leukemia Virus, Murine - metabolism; Mice; Microbiology; Molecular Sequence Data; Monkeys & apes; Murine leukemia virus; Oxides - metabolism; R Factors - genetics; R Factors - metabolism; Retroviridae - metabolism; Retroviridae Infections - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Sequence Alignment; Sequence Homology, Amino Acid
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0402474101

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.