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Journal of Virology, December 2008, p. 11495-11502, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01548-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The TRIM5{alpha} B-Box 2 Domain Promotes Cooperative Binding to the Retroviral Capsid by Mediating Higher-Order Self-Association{triangledown}

Xing Li1 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 22 July 2008/ Accepted 11 September 2008

The retroviral restriction factor, TRIM5{alpha}, blocks infection of a spectrum of retroviruses soon after virus entry into the cell. TRIM5{alpha} consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The B-box 2 domain is essential for retrovirus restriction by TRIM5{alpha}, but its specific function is unknown. We show here that the B-box 2 domain mediates higher-order self-association of TRIM5{alpha}rh oligomers. This self-association increases the efficiency of TRIM5{alpha} binding to the retroviral capsid, thus potentiating restriction of retroviral infection. The contribution of the B-box 2 domain to cooperative TRIM5{alpha} association with the retroviral capsid explains the conditional nature of the restriction phenotype exhibited by some B-box 2 TRIM5{alpha} mutants; the potentiation of capsid binding that results from B-box 2-mediated self-association is essential for restriction when B30.2(SPRY) domain-mediated interactions with the retroviral capsid are weak. Thus, B-box 2-dependent higher-order self-association and B30.2(SPRY)-dependent capsid binding represent complementary mechanisms whereby sufficiently dense arrays of capsid-bound TRIM5{alpha} proteins can be achieved.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute, 44 Binney Street-JFB 824, Boston, MA 02115. Phone: (617) 632-3371. Fax: (671) 632-4338. E-mail: joseph_sodroski{at}dfci.harvard.edu

{triangledown} Published ahead of print on 17 September 2008.

Journal of Virology, December 2008, p. 11495-11502, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01548-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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