Guarini School of Graduate and Advanced Studies, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
Virology. 2019 Mar;529:23-28. doi: 10.1016/j.virol.2019.01.006. Epub 2019 Jan 6.
Herpes simplex virus (HSV)- 1 is the most common cause of sporadic viral encephalitis and accounts for 5-10% of cases worldwide. A key factor in host control of viral infection is the initiation of the interferon (IFN) response, mediated in part by the stimulator of interferon genes (STING) pathway. In these studies, we examined the ability of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a STING agonist, to protect against HSV-1 infection. DMXAA reduced viral replication through increased production of type I IFN in vitro. Furthermore, administration of DMXAA to HSV-1 infected mice resulted in a reduction of viral burden in the peripheral and central nervous systems. This reduced viral burden also correlated with increased survival of DMXAA-treated infected mice. These results therefore demonstrate the potential of STING agonists for immunotherapy against HSV-1.
单纯疱疹病毒 1 型（HSV-1）是散发性病毒性脑炎最常见的病因，占全球病例的 5-10%。宿主控制病毒感染的一个关键因素是干扰素（IFN）反应的启动，部分由干扰素基因刺激物（STING）途径介导。在这些研究中，我们研究了 STING 激动剂 5,6-二甲基黄嘌呤-4-乙酸（DMXAA）预防 HSV-1 感染的能力。DMXAA 通过体外增加 I 型 IFN 的产生来减少病毒复制。此外，DMXAA 给药于 HSV-1 感染的小鼠可导致外周和中枢神经系统中病毒载量减少。这种病毒载量的减少也与 DMXAA 治疗感染小鼠的存活率增加相关。因此，这些结果表明 STING 激动剂在针对 HSV-1 的免疫治疗方面具有潜力。
