Trim5α accelerates degradation of cytosolic capsid associated with productive HIV-1 entry

The TRIM5 alpha(tripartite motif 5 alpha protein) has been linked to the cross-species restriction in human immunodeficiency virus type 1 (HIV-1) infection of non-human cells, but the mechanism by which this occurs remains to be fully elucidated. Here we demonstrate that the capsid (CA) protein of HIV-1 is more rapidly degraded in cells expressing monkey TRIM5 alpha than in cells expressing humanTRIM5 alpha. Other proteins encoded by Gag and Pol are not subject to TRIM5 alpha-mediated accelerated degradation. The accelerated CA degradation by TRIM5 alpha apparently occurs via a nonproteosomal pathway. TRIM5 alpha selectively accelerates degradation of the CA population, which reached the cytosol of restrictive cells, but not the CA population, which ended into the vesicular compartment. Given that cytosolic CA represents "productively" entered cores, whereas vesicular CA represents "nonproductively" entered cores, our findings suggest that TRIM5 alpha interrupts the infectious pathway of HIV-1 by acting on the incoming cytosolic CA. The mode of viral entry does not influence the accelerated degradation of cytosolic CA by TRIM5 alpha. Thus, this study reveals a correlation between TRIM5 alpha-mediated HIV-1 restriction and a selective degradation of cytosolic CA normally associated with productive viral entry.