Suppressor Of Cytokine Signaling 1 Counteracts Rhesus Macaque Trim5 Alpha-Induced Inhibition Of Human Immunodeficiency Virus Type-1 Production

Old world monkey TRIM5 alpha is a host factor that restricts human immunodeficiency virus type-1 (HIV-1) infection. Previously, we reported that rhesus macaque TRIM5 alpha (RhTRIM5 alpha) restricts HIV-1 production by inducing degradation of precursor Gag. Since suppressor of cytokine signaling 1 (SOCS1) is known to enhance HIV-1 production by rescuing Gag from lysosomal degradation, we examined if SOCS1 is involved in RhTRIM5 alpha-mediated late restriction. Over-expression of SOCS1 restored HIV-1 production in the presence of RhTRIM5 alpha to a level comparable to that in the absence of RhTRIM5 alpha in terms of titer and viral protein expression. Co-immunoprecipitation studies revealed that SOCS1 physically interacted with RhTRIM5 alpha. Over-expression of SOCS1 affected RhTRIM5 alpha expression in a dose-dependent manner, which was not reversed by proteasome inhibitors. In addition, SOCS1 and RhTRIM5 alpha were detected in virus-like particles. These results suggest that SOCS1 alleviates RhTRIM5 alpha-mediated regulation in the late phase of HIV-1 life cycle probably due to the destabilization of RhTRIM5 alpha.