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

The TRIM5α (tripartite motif 5α 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 TRIM5α than in cells expressing human TRIM5α. Other proteins encoded by Gag and Pol are not subject to TRIM5α-mediated accelerated degradation. The accelerated CA degradation by TRIM5α apparently occurs via a nonproteosomal pathway. TRIM5α 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 TRIM5α 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 TRIM5α. Thus, this study reveals a correlation between TRIM5α-mediated HIV-1 restriction and a selective degradation of cytosolic CA normally associated with productive viral entry.