Arsenic counteracts human immunodeficiency virus type 1 restriction by various TRIM5 orthologues in a cell type-dependent manner.
Arsenic trioxide (As(2)O(3)) 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 TRIM5alpha by RNA interference eliminated the As(2)O(3) 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 As(2)O(3), despite the potent TRIM5-dependent HIV-1 restriction activity that these cells exhibit. To determine if As(2)O(3) 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 As(2)O(3). In this context, the HIV-1 restriction activity conferred by all TRIM5 orthologues was largely eliminated by As(2)O(3). The effect of As(2)O(3) 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.
Sebastian
Sarah
S
Department of Microbiology, Columbia University, 701 West 168th Street, New York, NY 10032, USA.
Sokolskaja
Elena
E
Luban
Jeremy
J
D000818:Animals; D000090103:Antiviral Restriction Factors; D001029:Aotus trivirgatus; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D002415:Cats; D002460:Cell Line; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D020868:Gene Silencing; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development*; D006801:Humans; D008253:Macaca mulatta; D010087:Oxides / Q000494:pharmacology*; D034622:RNA Interference; D014161:Transduction, Genetic; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D001152:Arsenicals; D002352:Carrier Proteins; D018076:DNA, Complementary; D010087:Oxides; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D000077237:Arsenic Trioxide