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Herpes simplex virus-1 evasion of CD8+ T cell accumulation contributes to viral encephalitis
Naoto Koyanagi, … , Akihisa Kato, Yasushi Kawaguchi
Naoto Koyanagi, … , Akihisa Kato, Yasushi Kawaguchi
Published September 11, 2017
Citation Information: J Clin Invest. 2017;127(10):3784-3795. https://doi.org/10.1172/JCI92931.
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Research Article Virology

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

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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.

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

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Figure 5

Effect of HSV-1 UL13 kinase activity on expression of cytokine mRNAs in the infected brain stems of mice following ocular infection.

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Effect of HSV-1 UL13 kinase activity on expression of cytokine mRNAs in ...
Five-week-old female ICR mice were mock-infected or infected with 1 × 106 PFU UL13R or UL13KM per eye. At 7 days after infection, brain stem samples were processed, and the amounts of Cxcl9 (A), Cxcl10 (B), Cxcl11 (C), and Il-6 (D) mRNA were analyzed by quantitative RT-PCR. The results from 2 independent experiments (1 with 4 mice and 1 with 5 mice) were combined. Each data point is the relative amount of each mRNA in the brain stem of one mouse. The statistical significance values were analyzed by the Mann-Whitney U test.
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