Herpes simplex virus-1 evasion of CD8(+) T cell accumulation contributes to viral encephalitis

作者：Koyanagi Naoto; Imai Takahiko; Shindo Keiko; Sato Ayuko; Fujii Wataru; Ichinohe Takeshi; Takemura Naoki; Kakuta Shigeru; Uematsu Satoshi; Kiyono Hiroshi; Maruzuru Yuhei; Arii Jun; Kato Akihisa; Kawaguchi Yasushi^*

来源：Journal of Clinical Investigation, 2017, 127(10): 3784-3795.

DOI：10.1172/JCI92931

Herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis, which can be lethal or result in severe neurological defects even with antiviral therapy. While HSV-1 causes encephalitis in spite of HSV-1-specific humoral and cellular immunity, the mechanism by which HSV-1 evades the immune system in the central nervous system (CNS) remains unknown. Here we describe a strategy by which HSV-1 avoids immune targeting in the CNS. The HSV-1 UL13 kinase promotes evasion of HSV-1-specific CD8(+) T cell accumulation in infection sites by downregulating expression of the CD8(+) T cell attractant chemokine CXCL9 in the CNS of infected mice, leading to increased HSV-1 mortality due to encephalitis. Direct injection of CXCL9 into the CNS infection site enhanced HSV-1-specific CD8(+) T cell accumulation, leading to marked improvements in the survival of infected mice. This previously uncharacterized strategy for HSV-1 evasion of CD8(+) T cell accumulation in the CNS has important implications for understanding the pathogenesis and clinical treatment of HSV-1 encephalitis.

• 出版日期2017-10-2
• 单位河北医科大学