Yue Yujuan, Barry Peter A
Center for Comparative Medicine, University of California, Davis, California 95616, USA.
Adv Virus Res. 2008;72:207-26. doi: 10.1016/S0065-3527(08)00405-3.
Human cytomegalovirus (HCMV), a member of an ancient family of viruses (Herpesviridae), has acquired the capacity to maintain a lifelong persistent infection within an immunocompetent host. Since both primary and recurrent infections are generally subclinical, host antiviral immune responses are effective at limiting the pathogenic potential of HCMV. However, the fact that HCMV can persist in the presence of those protective immune responses indicates that host immunity is unable to prevent or eliminate long-term reservoirs of virus. The ability of HCMV to persist has important clinical implications, a fact reflected by the spectrum of pathogenic outcomes observed in those without a fully functional immune system. Recurrence of viral replication or transmission of HCMV from an infected individual to those most susceptible to primary infection during immune suppression, deficiency, or immaturity can lead to multiorgan disease and, sometimes, death. The clinical need for a protective HCMV vaccine has been recognized for decades, but due to a conspiracy of factors, there is no approved vaccine despite intensive investigations to develop one. Animal models of HCMV have been used as systems of discovery and translation to understand viral mechanisms of persistence and pathogenesis, and to test concepts and modalities for the generation of immune responses that protect from primary infection and sequelae. This review summarizes studies in a nonhuman primate model of HCMV involving infection of rhesus macaques (Macaca mulatta) with rhesus cytomegalovirus (RhCMV). The RhCMV model serves as an important complement to those in other animals, particularly small animals, and the lessons learned from RhCMV should have direct clinical relevance to HCMV and the design of protective vaccines.
人类巨细胞病毒（HCMV）是古老病毒家族（疱疹病毒科）的成员，已具备在免疫功能正常的宿主体内维持终身持续感染的能力。由于原发性和复发性感染通常都无明显临床症状，宿主的抗病毒免疫反应能够有效限制HCMV的致病潜力。然而，HCMV能在这些保护性免疫反应存在的情况下持续存在，这表明宿主免疫无法预防或消除病毒的长期储存库。HCMV持续存在的能力具有重要的临床意义，这一事实在那些免疫系统功能不全的个体所观察到的一系列致病结果中得到了体现。在免疫抑制、缺陷或不成熟期间，病毒复制的复发或HCMV从感染个体传播给最易发生原发性感染的个体，可导致多器官疾病，有时甚至死亡。数十年来，人们已经认识到临床需要一种保护性HCMV疫苗，但由于多种因素共同作用，尽管进行了大量开发研究，仍没有获批的疫苗。HCMV的动物模型已被用作发现和转化系统，以了解病毒持续存在和发病机制，并测试产生针对原发性感染和后遗症的保护性免疫反应的概念和方法。本综述总结了在HCMV的非人灵长类动物模型中进行的研究，该模型涉及用恒河猴巨细胞病毒（RhCMV）感染恒河猴（猕猴）。RhCMV模型是其他动物（尤其是小型动物）模型的重要补充，从RhCMV研究中吸取的经验教训应该与HCMV以及保护性疫苗的设计具有直接的临床相关性。
