T-Cell Vaccination Alters the Course of Murine Herpesvirus 68 Infection and the Establishment of Viral Latency in Mice

Diseases caused by gammaherpesviruses such as Epstein-Barr virus are a major health concern, and there is significant interest in developing vaccines against this class of viral infections. However, the requirements for effective control of gammaherpesvirus infection are only poorly understood. The recent development of the murine herpesvirus MHV-68 model provides an experimental tool to dissect the immune response to gammaherpesvirus infections. In this study, we investigated the impact of priming T cells specific for class I- and class II-restricted epitopes on the acute phase of the infection and the subsequent establishment of latency and infectious mononucleosis. The data show that vaccination with either major histocompatibility complex class I- or class II-restricted T-cell epitopes derived from lytic cycle proteins significantly reduced lung viral titers during the acute infection. Moreover, the peak level of latently infected spleen cells was significantly reduced following vaccination with immunodominant CD8(+) T-cell epitopes. However, this vaccination approach did not prevent the long-term establishment of latency or the development of the infectious mononucleosis-like syndrome in infected mice. Thus, the virus is able to establish latency efficiently despite strong immunological control of the lytic infection.

以EB病毒（Epstein-Barr virus）为代表的γ疱疹病毒（gammaherpesviruses）所引发的疾病是一类重大公共卫生问题，学界针对此类病毒感染开发疫苗的热情高涨。然而，当前人们对有效控制γ疱疹病毒感染的必要条件仍知之甚少。近期鼠疱疹病毒MHV-68（murine herpesvirus MHV-68）模型的构建，为解析γ疱疹病毒感染的免疫应答机制提供了实验工具。本研究探究了针对I类和II类限制性表位的特异性T细胞初免，对感染急性期、后续潜伏感染建立以及传染性单核细胞增多症发生的影响。实验数据显示，接种源自裂解周期蛋白的主要组织相容性复合体（major histocompatibility complex, MHC）I类或II类限制性T细胞表位疫苗，可显著降低急性感染期小鼠的肺部病毒滴度。此外，接种免疫显性CD8阳性T细胞表位后，潜伏感染脾细胞的峰值水平也显著降低。但该疫苗接种策略并未阻止潜伏感染在感染小鼠体内的长期建立，也未能阻止感染小鼠出现类传染性单核细胞增多症综合征。综上，即便机体对裂解感染实现了较强的免疫控制，病毒仍可高效建立潜伏感染。