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.
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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 |
Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 127
Issue 10
Pg. 3784-3795
(Oct 02 2017)
ISSN: 1558-8238 [Electronic] United States |
PMID | 28891812
(Publication Type: Journal Article)
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Chemical References |
- Chemokine CXCL9
- Cxcl9 protein, mouse
- Protein Kinases
- UL13 protein, Simplexvirus
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Topics |
- Animals
- CD8-Positive T-Lymphocytes
(immunology, pathology)
- Chemokine CXCL9
(genetics, immunology)
- Chlorocebus aethiops
- Encephalitis, Herpes Simplex
(genetics, immunology, pathology)
- Herpesvirus 1, Human
(genetics, immunology)
- Immune Evasion
- Immunity, Cellular
(genetics)
- Mice
- Mice, Knockout
- Protein Kinases
(immunology)
- Rabbits
- Vero Cells
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