Contribution of SUMO-interacting motifs and SUMOylation to the antiretroviral properties of TRIM5α

Recent findings suggested that the SUMO-interacting motifs (SIMs) present in the human TRIM5 alpha (TRIM5 alpha(hu)) protein play an important role in the ability of TRIM5 alpha(hu) to restrict N-MLV. Here we explored the role of SIMs in the ability of rhesus TRIM5 alpha (TRIM5 alpha(rh)) to restrict HIV-1, and found that TRIM5 alpha(rh) SIM mutants IL376KK (SIM1mut) and VI405KK (SIM2mut) completely lost their ability to block HIV-1 infection. Interestingly, these mutants also lost the recently described property of TRIM5 alpha(rh) to shuttle into the nucleus. Analysis of these variants revealed that they are unable to interact with the HIV-1 core, which might explain the reason that these variants are not active against HIV-1. Furthermore, NMR titration experiments to assay the binding between the PRYSPRY domain of TRIM5 alpha(th) and the small ubiquitin-like modifier 1(SUM0-1) revealed no interaction. In addition, we examined the role of SUMOylation in restriction, and find out that inhibition of SUMOylation by the adenoviral protein Gam1 did not alter the retroviral restriction ability of TRIM5 alpha. Overall, our results do not support a role for SIMs or SUMOylation in the antiviral properties of TRIM5 alpha. (C) 2012 Elsevier Inc. All rights reserved.