Blake N W, Moghaddam A, Rao P, Kaur A, Glickman R, Cho Y G, Marchini A, Haigh T, Johnson R P, Rickinson A B, Wang F
CRC Institute for Cancer Studies, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TA, United Kingdom.
J Virol. 1999 Sep;73(9):7381-9. doi: 10.1128/JVI.73.9.7381-7389.1999.
Most humans and Old World nonhuman primates are infected for life with Epstein-Barr virus (EBV) or closely related gammaherpesviruses in the same lymphocryptovirus (LCV) subgroup. Several potential strategies for immune evasion and persistence have been proposed based on studies of EBV infection in humans, but it has been difficult to test their actual contribution experimentally. Interest has focused on the EBV nuclear antigen 1 (EBNA1) because of its essential role in the maintenance and replication of the episomal viral genome in latently infected cells and because EBNA1 endogenously expressed in these cells is protected from presentation to the major histocompatibility complex class-I restricted cytotoxic T-lymphocyte (CTL) response through the action of an internal glycine-alanine repeat (GAR). Given the high degree of biologic conservation among LCVs which infect humans and Old World primates, we hypothesized that strategies essential for viral persistence would be well conserved among viruses of this subgroup. We show that the rhesus LCV EBNA1 shares sequence homology with the EBV and baboon LCV EBNA1 and that the rhesus LCV EBNA1 is a functional homologue for EBV EBNA1-dependent plasmid maintenance and replication. Interestingly, all three LCVs possess a GAR domain, but the baboon and rhesus LCV EBNA1 GARs fail to inhibit antigen processing and presentation as determined by using three different in vitro CTL assays. These studies suggest that inhibition of antigen processing and presentation by the EBNA1 GAR may not be an essential mechanism for persistent infection by all LCV and that other mechanisms may be important for immune evasion during LCV infection.
大多数人类和旧世界非人灵长类动物终生感染爱泼斯坦-巴尔病毒（EBV）或同一淋巴细胞性隐病毒（LCV）亚组中密切相关的γ疱疹病毒。基于对人类EBV感染的研究，已经提出了几种免疫逃避和持续存在的潜在策略，但很难通过实验来检验它们的实际作用。由于EBV核抗原1（EBNA1）在潜伏感染细胞中游离型病毒基因组的维持和复制中起着关键作用，并且这些细胞中内源性表达的EBNA1通过内部甘氨酸-丙氨酸重复序列（GAR）的作用，可免受主要组织相容性复合体I类限制性细胞毒性T淋巴细胞（CTL）反应的呈递，因此人们的兴趣集中在EBNA1上。鉴于感染人类和旧世界灵长类动物的LCV之间具有高度的生物学保守性，我们推测病毒持续存在所必需的策略在该亚组的病毒中会得到很好的保守。我们发现恒河猴LCV EBNA1与EBV和狒狒LCV EBNA1具有序列同源性，并且恒河猴LCV EBNA1是EBV EBNA1依赖性质粒维持和复制的功能同源物。有趣的是，所有三种LCV都具有一个GAR结构域，但通过三种不同的体外CTL检测确定，狒狒和恒河猴LCV EBNA1的GAR不能抑制抗原加工和呈递。这些研究表明，EBNA1的GAR对抗原加工和呈递的抑制作用可能不是所有LCV持续感染的必要机制，其他机制可能对LCV感染期间的免疫逃避很重要。
