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- Title
Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis.
- Authors
Naoto Koyanagi; Takahiko Imai; Keiko Shindo; Ayuko Sato; Wataru Fujii; Takeshi Ichinohe; Naoki Takemura; Shigeru Kakuta; Satoshi Uematsu; Hiroshi Kiyono; Yuhei Maruzuru; Jun Arii; Akihisa Kato; Yasushi Kawaguchi; Koyanagi, Naoto; Imai, Takahiko; Shindo, Keiko; Sato, Ayuko; Fujii, Wataru; Ichinohe, Takeshi
- Abstract
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.
- Subjects
HERPES simplex virus; VIRAL encephalitis; VIRUS diseases; ANTIVIRAL agents; CENTRAL nervous system; T cells
- Publication
Journal of Clinical Investigation, 2017, Vol 127, Issue 10, p3784
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI92931