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Host Factor SAMHD1 Restricts DNA Viruses in Non-Dividing Myeloid Cells
Authors:Joseph A Hollenbaugh  Peter Gee  Jonathon Baker  Michele B Daly  Sarah M Amie  Jessica Tate  Natsumi Kasai  Yuka Kanemura  Dong-Hyun Kim  Brian M Ward  Yoshio Koyanagi  Baek Kim
Institution:1. Department of Microbiology and Immunology, University of Rochester, Rochester, New York, United States of America.; 2. Center for Drug Discovery, The Department of Pediatrics, Emory University, Atlanta, Georgia, United States of America.; 3. Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.; 4. Department of Pharmacy, Kyung-Hee University, Seoul, South Korea.; University of Pennsylvania School of Medicine, United States of America,
Abstract:SAMHD1 is a newly identified anti-HIV host factor that has a dNTP triphosphohydrolase activity and depletes intracellular dNTP pools in non-dividing myeloid cells. Since DNA viruses utilize cellular dNTPs, we investigated whether SAMHD1 limits the replication of DNA viruses in non-dividing myeloid target cells. Indeed, two double stranded DNA viruses, vaccinia and herpes simplex virus type 1, are subject to SAMHD1 restriction in non-dividing target cells in a dNTP dependent manner. Using a thymidine kinase deficient strain of vaccinia virus, we demonstrate a greater restriction of viral replication in non-dividing cells expressing SAMHD1. Therefore, this study suggests that SAMHD1 is a potential innate anti-viral player that suppresses the replication of a wide range of DNA viruses, as well as retroviruses, which infect non-dividing myeloid cells.
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