Mühe Janine, Wang Fred
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, 181 Longwood Ave, Boston, MA, 02115.
Department of Molecular Biology and Immunobiology, Harvard Medical School, Brigham and Women's Hospital, 181 Longwood Ave, Boston, MA, 02115.
Curr Top Microbiol Immunol. 2015;391:385-405. doi: 10.1007/978-3-319-22834-1_13.
Epstein-Barr virus (EBV) orthologues from non-human primates (NHPs) have been studied for nearly as long as EBV itself. Cross-reactive sera and DNA hybridization studies provided the first glimpses of the closely related herpesviruses that belonged to the same gamma-1 herpesvirus, or lymphocryptovirus, genus, as EBV. Over the years, detailed molecular and sequence analyses of LCVs that infect humans and other NHPs revealed similar colinear genome structures and homologous viral proteins expressed during latent and lytic infection. Despite these similarities, experimental infection of NHPs with EBV did not result in acute symptoms or persistent infection as observed in humans, suggesting some degree of host species restriction. Genome sequencing and a molecular clone of an LCV isolate from naturally infected rhesus macaques combined with domestic colonies of LCV-naïve rhesus macaques have opened the door to a unique experimental animal model that accurately reproduces the normal transmission, acute viremia, lifelong persistence, and immune responses found in EBV-infected humans. This chapter will summarize the advances made over the last 50 years in our understanding of LCVs that naturally infect both Old and New World NHPs, the recent, groundbreaking developments in the use of rhesus macaques as an animal model for EBV infection, and how NHP LCVs and the rhLCV animal model can advance future EBV research and the development of an EBV vaccine.
对来自非人灵长类动物（NHPs）的爱泼斯坦-巴尔病毒（EBV）直系同源物的研究时间几乎与对EBV本身的研究时间一样长。交叉反应血清和DNA杂交研究首次让人们了解到这些与EBV同属γ-1疱疹病毒属（即淋巴细胞性脉络丛脑膜炎病毒属）的密切相关的疱疹病毒。多年来，对感染人类和其他非人灵长类动物的淋巴细胞性脉络丛脑膜炎病毒（LCVs）进行的详细分子和序列分析揭示了相似的共线性基因组结构以及在潜伏感染和裂解感染期间表达的同源病毒蛋白。尽管存在这些相似之处，但用EBV对非人灵长类动物进行实验性感染并未像在人类中观察到的那样导致急性症状或持续感染，这表明存在一定程度的宿主物种限制。对从自然感染的恒河猴中分离出的一种LCV分离株进行基因组测序并获得分子克隆，再结合未感染LCV的恒河猴的家养群体，这为一种独特的实验动物模型打开了大门，该模型能准确再现EBV感染人类时的正常传播、急性病毒血症、终身持续性感染以及免疫反应。本章将总结过去50年里我们在理解自然感染新旧世界非人灵长类动物的LCVs方面取得的进展、将恒河猴用作EBV感染动物模型的最新突破性进展，以及非人灵长类动物LCVs和恒河猴LCV动物模型如何推动未来的EBV研究和EBV疫苗的开发。
