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Journal of Virology, March 2007, p. 2138-2148, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.02318-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Human TRIM5{alpha} Restriction Factor Mediates Accelerated Uncoating of the N-Tropic Murine Leukemia Virus Capsid{triangledown}

Michel J. Perron,1 Matthew Stremlau,1 Mark Lee,1 Hassan Javanbakht,1 Byeongwoon Song,1 and Joseph Sodroski1,2*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 021152

Received 23 October 2006/ Accepted 20 November 2006

The host cell factors TRIM5{alpha}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 TRIM5{alpha}hu and Fv-1. In this study, we investigate the fate of the MLV capsid in cells expressing either the TRIM5{alpha}hu or Fv-1 restriction factor. The expression of TRIM5{alpha}hu, but not Fv-1, specifically promoted the premature conversion of particulate N-MLV capsids within infected cells to soluble capsid proteins. The TRIM5{alpha}hu-mediated disassembly of particulate N-MLV capsids was dependent upon residue 110 of the viral capsid. Furthermore, the deletion or disruption of TRIM5{alpha}hu domains necessary for potent N-MLV restriction completely abrogated the disappearance of particulate N-MLV capsids observed with wild-type TRIM5{alpha}hu. These results suggest that premature disassembly of the viral capsid contributes to the restriction of N-MLV infection by TRIM5{alpha}hu, but not by Fv-1.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115. Phone: (617) 632-3371. Fax: (617) 632-4338. E-mail: joseph_sodroski{at}dfci.harvard.edu.

{triangledown} Published ahead of print on 29 November 2006.

Journal of Virology, March 2007, p. 2138-2148, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.02318-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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