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Journal of Virology, December 2005, p. 15567-15572, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15567-15572.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Restriction of Human Immunodeficiency Virus Type 1 by TRIM-CypA Occurs with Rapid Kinetics and Independently of Cytoplasmic Bodies, Ubiquitin, and Proteasome Activity

David Perez-Caballero,{dagger} Theodora Hatziioannou,{dagger} Fengwen Zhang, Simone Cowan, and Paul D. Bieniasz*

Aaron Diamond AIDS Research Center and the Rockefeller University, New York, New York

Received 29 June 2005/ Accepted 21 September 2005

TRIM-CypA is an owl monkey-specific variant of the retrovirus restriction factor TRIM5{alpha}. Here, we exploit its modular domain organization and cyclosporine sensitivity to probe the kinetics and mechanism of TRIM5-mediated restriction. Time of addition/withdrawal experiments reveal that inhibition of incoming human immunodeficiency virus type 1 capsids by TRIM-CypA occurs within minutes of their delivery to the target cell cytoplasm. However, while TRIM-CypA restriction is partly dependent on a RING domain, restriction occurs independently of the ubiquitin/proteasome system. Moreover, tagged TRIM-CypA proteins can be fully active as restriction factors without forming cytoplasmic bodies.

* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016. Phone: (212) 448-5070. Fax: (212) 725-1126. E-mail: pbienias{at}adarc.org.

{dagger} D.P-C. and T.H. contributed equally to this work.

Journal of Virology, December 2005, p. 15567-15572, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15567-15572.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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