The Modulation of Phosphatase Expression Impacts the Proliferation Efficiency of HSV-1 in Infected Astrocytes |
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| Authors: | Lei Yue Sujie Guo Ying Zhang Longding Liu Qingling Wang Xi Wang Dong Shen Lichun Wang Le Sun Jingjing Wang Yun Liao Qihan Li |
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| Institution: | Institute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Kunming, People’s Republic of China.; University of Pennsylvania School of Veterinary Medicine, United States of America, |
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| Abstract: | Herpes Simplex Virus 1 (HSV-1) is a major pathogen that causes human neurological diseases, including herpes simplex encephalitis (HSE). Previous studies have shown that astrocytes are involved in HSV-1 systemic pathogenesis in the central nervous system (CNS), although the mechanism remains unclear. In this study, a high-throughput RNAi library screening method was used to analyze the effect of host phosphatase gene regulation on HSV-1 replication using Macaca mulatta primary astrocytes in an in vitro culture system. The results showed that the downregulation of five phosphatase genes (PNKP, SNAP23, PTPRU, LOC714621 and PPM1M) significantly inhibited HSV-1 infection, suggesting that these phosphatases were needed in HSV-1 replication in rhesus astrocytes. Although statistically significant, the effect of downregulation of these phosphatases on HSV-1 replication in a human astrocytoma cell line appears to be more limited. Our results suggest that the phosphatase genes in astrocytes may regulate the immunological and pathological reactions caused by HSV-1 CNS infection through the regulation of HSV-1 replication or of multiple signal transduction pathways. |
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