The Human TRIM5α Restriction Factor Mediates Accelerated Uncoating of the N-Tropic Murine Leukemia Virus Capsid

Abstract

ABSTRACT The host cell factors TRIM5α hu and Fv-1 restrict N-tropic murine leukemia virus (N-MLV) infection at an early postentry step before or after reverse transcription, respectively. Interestingly, the identity of residue 110 of the MLV capsid determines susceptibility to both TRIM5α hu and Fv-1. In this study, we investigate the fate of the MLV capsid in cells expressing either the TRIM5α hu or Fv-1 restriction factor. The expression of TRIM5α hu , but not Fv-1, specifically promoted the premature conversion of particulate N-MLV capsids within infected cells to soluble capsid proteins. The TRIM5α hu -mediated disassembly of particulate N-MLV capsids was dependent upon residue 110 of the viral capsid. Furthermore, the deletion or disruption of TRIM5α hu domains necessary for potent N-MLV restriction completely abrogated the disappearance of particulate N-MLV capsids observed with wild-type TRIM5α hu . These results suggest that premature disassembly of the viral capsid contributes to the restriction of N-MLV infection by TRIM5α hu , but not by Fv-1.