TY - JOUR
T1 - Contribution of SUMO-interacting motifs and SUMOylation to the antiretroviral properties of TRIM5α
AU - Brandariz-Nuñez, Alberto
AU - Roa, Amanda
AU - Valle-Casuso, Jose Carlos
AU - Biris, Nikolaos
AU - Ivanov, Dmitri
AU - Diaz-Griffero, Felipe
N1 - Funding Information:
We thank Andre Rosowsky for critical reading of the manuscript. We thank Dr. Andrei Tomashevski for his help with recombinant protein purification. We thank Susanna Chiocca for providing reagents. This work was funded by the NIH No. R01 AI087390 to F.D.-G, CPRIT Scholar Award to D.I. and a K99/R00 Pathway to Independence Award to F.D.-G. from the National Institutes of Health No. 4R00MH086162-02 .
PY - 2013/1/20
Y1 - 2013/1/20
N2 - 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.
AB - 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.
KW - HIV-1
KW - Restriction
KW - SUMO-interacting motif
KW - SUMOylation
KW - TRIM5α
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U2 - 10.1016/j.virol.2012.09.042
DO - 10.1016/j.virol.2012.09.042
M3 - Article
C2 - 23084420
AN - SCOPUS:84871706030
SN - 0042-6822
VL - 435
SP - 463
EP - 471
JO - Virology
JF - Virology
IS - 2
ER -