Arsenic Counteracts Human Immunodeficiency Virus Type 1 Restriction by Various TRIM5 Orthologues in a Cell Type-Dependent Manner

Arsenic trioxide (As2 O3 ) increased human immunodeficiency virus type 1 (HIV-1) infectivity when particularHomo sapiens andCercopithecus aethiops cell lines were used as targets. Knockdown of human TRIM5α by RNA interference eliminated the As2 O3 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 , andAotus trivirgatus ) was not increased by As2 O3 , despite the potent TRIM5-dependent HIV-1 restriction activity that these cells exhibit. To determine if As2 O3 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 As2 O3 . In this context, the HIV-1 restriction activity conferred by all TRIM5 orthologues was largely eliminated by As2 O3 . The effect of As2 O3 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.