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Journal of Virology, February 2006, p. 2051-2054, Vol. 80, No. 4
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.4.2051-2054.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Departments of Microbiology,1 Medicine, Columbia University, 701 West 168th Street, New York, New York 100322
Received 19 August 2005/ Accepted 21 November 2005
Arsenic trioxide (As2O3) increased human immunodeficiency virus type 1 (HIV-1) infectivity when particular Homo sapiens and Cercopithecus aethiops cell lines were used as targets. Knockdown of human TRIM5
by RNA interference eliminated the As2O3 effect, demonstrating that the drug acts by modulating the activity of this retroviral restriction factor. In contrast, HIV-1 infectivity in target cell lines from other primate species (Cercopithecus tantalus, Macaca mulatta, and Aotus trivirgatus) was not increased by As2O3, despite the potent TRIM5-dependent HIV-1 restriction activity that these cells exhibit. To determine if As2O3 responsiveness is characteristic of particular TRIM5 orthologues and not others, TRIM5 cDNAs from these five primate species were transduced into cat fibroblasts, which lack endogenous HIV-1 restriction activity and, therefore, responsiveness to As2O3. In this context, the HIV-1 restriction activity conferred by all TRIM5 orthologues was largely eliminated by As2O3. The effect of As2O3 on HIV-1 restriction is thus shared by different TRIM5 orthologues but dependent on factors specific to the cell line in which TRIM5 is expressed.
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