The human and African green monkey TRIM5α genes encode Ref1 and Lv1 retroviral restriction factor activities

The rhesus macaque tripartite motif containing protein TRIM5α 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) TRIM5α genes encode Ref1 and Lv1 antiretroviral activities, respectively. Expression of TRIM5α in permissive cat cells renders them resistant to restriction-sensitive murine leukemia virus but not closely related insensitive virus. Disruption of TRIM5α 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 TRIM5α 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 TRIM5α. Alignment of the TRIM5α 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 TRIM5α restriction as compared with the human and rhesus macaque proteins.