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.

中文翻译：

---

单纯疱疹病毒1逃逸的CD8 ⁺ T细胞积累助长了病毒性脑炎

单纯疱疹病毒-1（HSV-1）是偶发性病毒性脑炎的最常见原因，即使使用抗病毒治疗，也可能致命或导致严重的神经系统缺陷。尽管HSV-1具有特定的体液和细胞免疫功能，但HSV-1仍会引起脑炎，但HSV-1逃避中枢神经系统（CNS）免疫系统的机制仍然未知。在这里，我们描述了HSV-1避免在CNS中进行免疫靶向的策略。HSV-1 UL13激酶通过下调CD8 ^+的表达来促进逃逸HSV-1特异性CD8 ⁺ T细胞在感染部位的蓄积。T细胞引诱趋化因子CXCL9在感染小鼠的中枢神经系统中，导致因脑炎引起的HSV-1死亡率增加。将CXCL9直接注射到CNS感染部位可增强HSV-1特异性CD8 ⁺ T细胞的积累，从而显着改善被感染小鼠的存活率。HSS-1逃避中枢神经系统中CD8 ⁺ T细胞积累的HSV-1逃避策略，对于理解HSV-1脑炎的发病机理和临床治疗具有重要意义。