Lineberger Cancer Research Center and Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27514, USA.
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
FEMS Microbiol Rev. 2019 Mar 1;43(2):181-192. doi: 10.1093/femsre/fuy044.
Human γ-herpesviruses include the closely related tumor viruses Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). EBV is the most growth-transforming pathogen known and is linked to at least seven human malignancies. KSHV is also associated with three human cancers. Most EBV- and KSHV-infected individuals fortunately remain disease-free despite persistent infection and this is likely due to the robustness of the immune control that they mount against these tumor viruses. However, upon immune suppression EBV- and KSHV-associated malignancies emerge at increased frequencies. Moreover, primary immunodeficiencies with individual mutations that predispose to EBV or KSHV disease allow us to gain insights into a catalog of molecules that are required for the immune control of these tumor viruses. Curiously, there is little overlap between the mutation targets that predispose individuals to EBV versus KSHV disease, even so both viruses can infect the same host cell, human B cells. These differences will be discussed in this review. A better understanding of the crucial components in the near-perfect life-long immune control of EBV and KSHV should allow us to target malignancies that are associated with these viruses, but also induce similar immune responses against other tumors.
人类 γ-疱疹病毒包括密切相关的肿瘤病毒 EBV（Epstein Barr virus，EB 病毒）和卡波西肉瘤相关疱疹病毒（Kaposi sarcoma-associated herpesvirus，KSHV）。EBV 是已知最具生长转化能力的病原体，与至少七种人类恶性肿瘤有关。KSHV 也与三种人类癌症有关。尽管存在持续性感染，但大多数 EBV 和 KSHV 感染个体仍保持无病状态，这可能是由于他们对这些肿瘤病毒产生了强大的免疫控制。然而，在免疫抑制的情况下，EBV 和 KSHV 相关的恶性肿瘤出现的频率增加。此外，个体突变导致的原发性免疫缺陷使 EBV 或 KSHV 发病，使我们能够深入了解免疫控制这些肿瘤病毒所需的分子目录。奇怪的是，导致个体易患 EBV 与 KSHV 疾病的突变靶点几乎没有重叠，尽管如此，这两种病毒都可以感染相同的宿主细胞，即人类 B 细胞。本综述将讨论这些差异。更好地了解 EBV 和 KSHV 近乎完美的终身免疫控制的关键组成部分，应该使我们能够针对与这些病毒相关的恶性肿瘤，并诱导针对其他肿瘤的类似免疫反应。
