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 TRIM5α (TRIM5αhu) protein play an important role in the ability of TRIM5αhu to restrict N-MLV. Here we explored the role of SIMs in the ability of rhesus TRIM5α (TRIM5αrh) to restrict HIV-1, and found that TRIM5αrh 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 TRIM5αrh 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 TRIM5αrh and the small ubiquitin-like modifier 1(SUMO-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 TRIM5α. Overall, our results do not support a role for SIMs or SUMOylation in the antiviral properties of TRIM5α.