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Journal of Virology, July 2006, p. 6738-6744, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.00270-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Removal of Arginine 332 Allows Human TRIM5{alpha} To Bind Human Immunodeficiency Virus Capsids and To Restrict Infection

Yuan Li,1 Xing Li,1 Matthew Stremlau,1 Mark Lee,1 and Joseph Sodroski1,2*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, 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 7 February 2006/ Accepted 8 May 2006

Human TRIM5{alpha} (TRIM5{alpha}hu) only modestly inhibits human immunodeficiency virus type 1 (HIV-1) and does not inhibit simian immunodeficiency virus (SIVmac). Alteration of arginine 332 in the TRIM5{alpha}hu B30.2 domain to proline, the residue found in rhesus monkey TRIM5{alpha}, has been shown to create a potent restricting factor for both HIV-1 and SIVmac. Here we demonstrate that the potentiation of HIV-1 inhibition results from the removal of a positively charged residue at position 332 of TRIM5{alpha}hu. The increase in restricting activity correlated with an increase in the ability of TRIM5{alpha}hu mutants lacking arginine 332 to bind HIV-1 capsid complexes. A change in the cyclophilin A-binding loop of the HIV-1 capsid decreased TRIM5{alpha}hu R332P binding and allowed escape from restriction. The ability of TRIM5{alpha}hu to restrict SIVmac could be disrupted by the presence of any charged residue at position 332. Thus, charged residues in the v1 region of the TRIM5{alpha}hu B30.2 domain can modulate capsid binding and restriction potency. Therapeutic strategies designed to neutralize arginine 332 of TRIM5{alpha}hu might potentiate the innate resistance of human cells to HIV-1 infection.

* Corresponding author. Mailing address: Department of Cancer Immunology and AIDS, 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.

Journal of Virology, July 2006, p. 6738-6744, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.00270-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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