Viral Immunobiology, Institute of Experimental Immunology, University of Zürich , Switzerland.
Philos Trans R Soc Lond B Biol Sci. 2019 May 27;374(1773):20180296. doi: 10.1098/rstb.2018.0296.
Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) comprise the oncogenic human γ-herpesvirus family and are responsible for 2-3% of all tumours in man. With their prominent growth-transforming abilities and high prevalence in the human population, these pathogens have probably shaped the human immune system throughout evolution for near perfect immune control of the respective chronic infections in the vast majority of healthy pathogen carriers. The exclusive tropism of EBV and KSHV for humans has, however, made it difficult in the past to study their infection, tumourigenesis and immune control in vivo. Mice with reconstituted human immune system components (humanized mice) support replication of both viruses with both persisting latent and productive lytic infection. Moreover, B-cell lymphomas can be induced by EBV alone and KSHV co-infection with gene expression hallmarks of human malignancies that are associated with both viruses. Furthermore, cell-mediated immune control by primarily cytotoxic lymphocytes is induced upon infection and can be probed for its functional characteristics as well as putative requirements for its priming. Insights that have been gained from this model and remaining questions will be discussed in this review. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
爱泼斯坦-巴尔病毒 (EBV) 和卡波西肉瘤相关疱疹病毒 (KSHV) 属于致癌性人类 γ-疱疹病毒家族，占人类所有肿瘤的 2-3%。由于它们具有明显的生长转化能力和在人类中的高流行率，这些病原体在进化过程中可能塑造了人类免疫系统，以便在绝大多数健康病原体携带者中对各自的慢性感染进行近乎完美的免疫控制。然而，EBV 和 KSHV 对人类的独特嗜性使得过去难以在体内研究它们的感染、肿瘤发生和免疫控制。具有重建的人类免疫系统成分的小鼠（人源化小鼠）支持两种病毒的复制，既有持续潜伏的感染，也有活跃的裂解感染。此外，EBV 单独感染可诱导 B 细胞淋巴瘤，而 KSHV 合并感染则伴有与两种病毒相关的人类恶性肿瘤的基因表达特征。此外，感染后会诱导细胞介导的免疫控制，可以对其功能特征以及其引发所需的条件进行探测。本综述将讨论从该模型中获得的见解和仍然存在的问题。本文是主题为“沉默的致癌因子：人类 DNA 致癌病毒的多学科建模”的一部分。
