SAMHD1 Suppresses Innate Immune Responses to Viral Infections and Inflammatory Stimuli by Inhibiting the NF-Κb and Interferon Pathways
SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-κB and interferon pathways Shuliang Chena,b,1, Serena Bonifatia,1, Zhihua Qina, Corine St. Gelaisa, Karthik M. Kodigepallia, Bradley S. Barrettc, Sun Hee Kima, Jenna M. Antonuccia, Katherine J. Ladnerd,e, Olga Buzovetskyf, Kirsten M. Knechtf, Yong Xiongf, Jacob S. Yountg, Denis C. Guttridged,e, Mario L. Santiagoc, and Li Wua,e,g,2 aCenter for Retrovirus Research, Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210; bSchool of Basic Medical Sciences, Wuhan University, 430071 Wuhan, People’s Republic of China; cDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO 80045; dDepartment of Cancer Biology and Genetics, Ohio State University, Columbus, OH 43210; eComprehensive Cancer Center, Ohio State University, Columbus, OH 43210; fDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520; and gDepartment of Microbial Infection and Immunity, Ohio State University, Columbus, OH 43210 Edited by Robert F. Siliciano, Johns Hopkins University School of Medicine, Baltimore, MD, and approved March 16, 2018 (received for review January 25, 2018) Sterile alpha motif and HD-domain–containing protein 1 (SAMHD1) have reported spontaneous induction of ISG transcripts in blocks replication of retroviruses and certain DNA viruses by reduc- SAMHD1-deficient mouse cells (17–19) and hyperactivity of the ing the intracellular dNTP pool. SAMHD1 has been suggested to IFN-I pathway in mouse macrophages with SAMHD1 knock- down-regulate IFN and inflammatory responses to viral infections, down (20). Although SAMHD1 has been implicated in nega- although the functions and mechanisms of SAMHD1 in modulating tively regulating IFN-I and inflammation responses (15, 17, 19), innate immunity remain unclear.
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