The Modulation of Phosphatase Expression Impacts the Proliferation Efficiency of HSV-1 in Infected Astrocytes

<div><p>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 <i>Macaca mulatta</i> primary astrocytes in an <i>in vitro</i> 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.</p>