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Journal of Virology, June 2005, p. 7883-7888, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7883-7888.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Disruption of Human TRIM5{alpha} Antiviral Activity by Nonhuman Primate Orthologues

Lionel Berthoux,1 Sarah Sebastian,1 David M. Sayah,1 and Jeremy Luban1,2*

Departments of Microbiology,1 Medicine, Columbia University College of Physicians and Surgeons, 701 West 168th Street, New York, New York 100322

Received 16 September 2004/ Accepted 15 February 2005

TRIM5 is a determinant of species-specific differences in susceptibility to infection by retroviruses bearing particular capsids. Human immunodeficiency virus type 1 (HIV-1) infection is blocked by the alpha isoform of macaque TRIM5 (TRIM5{alpha}rh) or by the product of the owl monkey TRIM5-cyclophilin A gene fusion (TRIMCyp). Human TRIM5{alpha} potently restricts specific strains of murine leukemia virus (N-MLV) but has only a modest effect on HIV-1. The amino termini of TRIM5 orthologues are highly conserved and possess a coiled-coil domain that promotes homomultimerization. Here we show that heterologous expression of TRIM5{alpha}rh or TRIMCyp in human cells interferes with the anti-N-MLV activity of endogenous human TRIM5{alpha} (TRIM5{alpha}hu). Deletion of the cyclophilin domain from TRIMCyp has no effect on heteromultimerization or colocalization with TRIM5{alpha}hu but prevents interference with anti-N-MLV activity. These data demonstrate that TRIM5 orthologues form heteromultimers and indicate that C-terminal extensions alter virus recognition by multimers of these proteins.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 West 168th St., New York, NY 10032. Phone: (212) 305-8706. Fax: (212) 305-0333. E-mail: JL45{at}columbia.edu.

Journal of Virology, June 2005, p. 7883-7888, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7883-7888.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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