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SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity

Nature Medicine volume 22, pages 1072–1074 (2016)Cite this article

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Sterile alpha motif domain– and HD domain–containing protein 1 (SAMHD1) is a cellular dNTP triphosphohydrolase (dNTPase) that restricts HIV-1 replication in myeloid cells and resting CD4+ T cells by degrading dNTPs and limiting viral reverse transcription1,2,3,4,5. Purified recombinant SAMHD1 also has exonuclease activity when synthetic nucleic acids or HIV-1 gag and tat RNAs transcribed in vitro are used as substrates6. Ryoo et al.7 recently suggested that SAMHD1 restricts HIV-1 infection through its ribonuclease (RNase) activity by cleaving the viral RNA genome. By using SAMHD1 mutants purported to specifically retain dNTPase (SAMHD1Q548A) or RNase (SAMHD1D137N) activities, Ryoo et al.7,8 proposed that the RNase activity of SAMHD1, but not its dNTPase activity, is essential for HIV-1 restriction in nondividing cells. They also suggested that SAMHD1 phosphorylation at T592 negatively regulated its RNase activity7.

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Figure 1: SAMHD1-mediated HIV-1 restriction in cells does not involve RNase activity.

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Acknowledgements

This work was supported by NIH grants AI104483 and CA181997 (L.W.), AI114826 (J.S.Y.), AI102778 (Y.X.), AI120845 (X.J.) and AI049781 and GM104198 (B.K.). The authors thank N. Landau for the pLenti-puro plasmids, and J. Hach and S.H. Kim for technical assistance. The antibody to HIV-1 p24 Gag (clone #24-2) and nevirapine were obtained from the NIH AIDS Reagent Program.

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  1. Suresh de Silva

    Present address: Present address: Heat Biologics, Durham, North Carolina, USA.,

Authors and Affiliations

  1. Department of Veterinary Biosciences, Center for Retrovirus Research, Ohio State University, Columbus, Ohio, USA

    Jenna M Antonucci, Corine St. Gelais, Suresh de Silva & Li Wu

  2. Department of Microbiology, Ohio State University, Columbus, Ohio, USA

    Jenna M Antonucci & Li Wu

  3. Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA

    Jacob S Yount & Li Wu

  4. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, USA

    Chenxiang Tang, Xiaoyun Ji & Yong Xiong

  5. Department of Pediatrics, Center for Drug Discovery, Emory University School of Medicine, Atlanta, Georgia, USA

    Caitlin Shepard & Baek Kim

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Contributions

J.M.A., C.S.G., S.d.S., J.S.Y., Y.X. and L.W. designed the study and wrote the manuscript. J.M.A., C.S.G., S.d.S., C.T., X.J. and C.S. performed the experiments and analyses. J.M.A, C.S.G., S.d.S., J.S.Y., Y.X., B.K. and L.W. analyzed the data. All authors discussed the data and approved the manuscript.

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Correspondence to Li Wu.

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Antonucci, J., St. Gelais, C., de Silva, S. et al. SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity. Nat Med 22, 1072–1074 (2016). https://doi.org/10.1038/nm.4163

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