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 (TRIM5α(hu)) protein play an important role in the ability of TRIM5α(hu) to restrict N-MLV. Here we explored the role of SIMs in the ability of rhesus TRIM5α (TRIM5α(rh)) to restrict HIV-1, and found that TRIM5α(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 TRIM5α(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 TRIM5α(rh) 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.
Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461, USA.
Alberto
A
Brandariz-Nuñez
Amanda
A
Roa
Jose Carlos
JC
Valle-Casuso
Nikolaos
N
Biris
Dmitri
D
Ivanov
Felipe
F
Diaz-Griffero
D020816:Amino Acid Motifs; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009154:Mutation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D025842:SUMO-1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014162:Transfection; D044767:Ubiquitin-Protein Ligases
D000998:Antiviral Agents; D011506:Proteins; D025842:SUMO-1 Protein; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases