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.
Highlights
Herpes Simplex Virus 1 (HSV-1), a DNA virus with a complex gene expression program [1], can manipulate transcription regulation leading to latent infection [2], and cause comprehensive pathological injury, such as herpes simplex encephalitis (HSE) with poor prognosis, in hosts during its infection process [3,4]
This study investigated the interaction between HSV-1 and cellular phosphatases involved in the regulation of HSV-1 infection using siRNA interference of 212 phosphatases in astrocytes to observe the titer changes in HSV-1
This observation was extended to human astrocytoma cells, in which the downregulation of these five phosphatases inhibited the proliferation of HSV-1 and implied a role of these five phosphatases in the replication of HSV-1 in astrocytes
Summary
Herpes Simplex Virus 1 (HSV-1), a DNA virus with a complex gene expression program [1], can manipulate transcription regulation leading to latent infection [2], and cause comprehensive pathological injury, such as herpes simplex encephalitis (HSE) with poor prognosis, in hosts during its infection process [3,4]. Previous studies have shown that astrocytes in the central nervous system (CNS) are involved in the pathogenesis of HSV-1 encephalitis [7]. This involvement occurs because astrocytes, with a fast response to invasive pathogens [8], are important immune cells in the CNS, and because of the capability of HSV-1 to infect astrocytes and promote systemic pathogenesis in the CNS [9]. To explore the role of certain phosphatases in HSV-1 replication might be helpful to yield insight into the cellular response to viral infection and into their further significance in the pathogenesis of HSV-1 infection in astrocytes, which is a part of the pathological process of encephalitis induced by this virus [13]. Our work in this study was focused on the interaction of phosphatases with HSV-1 in astrocytes to better understand the molelular mechanism HSV-1 pathogenesis in infectious encephalitis
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