Defining the mechanisms that regulate effective long-term anti-viral immunity

人巨细胞病毒（HCMV）是一种常见的人类病原体，通常会引起轻度甚至无症状的感染。然而，在免疫功能低下的个体中，HCMV引起严重的疾病，其表现包括脉络膜视网膜炎、间质性肺炎和肝炎。同样，在缺乏完全成熟的免疫系统的新生儿中，HCMV导致严重的发病率。预防HCMV诱导的巨细胞包涵体病的疫苗被指定为I级（最有利），因为预测它们可以挽救生命并预防终身残疾。同样，预防和/或减少HCMV再活化的治疗将显著改善移植和艾滋病患者的预后。鼠CMV（MCMV）感染模型提供了关于免疫系统如何控制感染以及病毒利用机制来规避这些过程的重要见解。设计有效的疗法和疫苗需要彻底了解产生和维持持久抗病毒反应所需的机制。本提案中概述的研究旨在确定免疫系统特定组分对抗病毒免疫的产生、维持和有效性的影响。将使用充分表征的MCMV模型来解决这些问题。

Human cytomegalovirus (HCMV) is a common human pathogen which normally causes a mild or even asymptomatic infection. However, in immunocompromised individuals, HCMV causes severe disease whose manifestations include chorioretinitis, interstitial pneumonia and hepatitis. Similarly, in neonates lacking a fully mature immune system, HCMV causes severe morbidity. Vaccines that protect against HCMV induced cytomegalic inclusion disease have been designated Level I (most favourable) due to the prediction that they could save lives and prevent life-long disability. Similarly, therapies that prevent and-or reduce HCMV reactivation will significantly improve the prognosis of transplant and AIDS patients. The murine CMV (MCMV) infection model has provided important insights as to how the immune system controls infection, and the mechanisms utilized by the virus to circumvent these processes. The design of effective therapies and vaccines requires a thorough understanding of the mechanisms required to generate and maintain long-lasting anti-viral responses. The studies outlined in this proposal aim to define the impact of specific components of the immune system n the generation, maintenance and effectiveness of anti-viral immunity. The well characterized MCMV model will be used to address these issues.