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

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.sup.+] T cell accumulation in infection sites by downregulating expression of the [CD8.sup.+] 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.sup.+] T cell accumulation, leading to marked improvements in the survival of infected mice. This previously uncharacterized strategy for HSV-1 evasion of [CD8.sup.+] T cell accumulation in the CNS has important implications for understanding the pathogenesis and clinical treatment of HSV-1 encephalitis.
Introduction HSV-1 is generally associated with various mucocutaneous diseases, such as herpes labialis, genital herpes, herpetic whitlow, and keratitis (1). Also, HSV-1 is the most common cause of sporadic viral [...]