人类疱疹病毒8型的免疫逃逸分子机制

The molecular mechanism of immune evasion of human herpesvirus 8

摘要:

人类疱疹病毒8型(human herpesvirus 8, HHV-8)又称卡波西肉瘤相关疱疹病毒(Kaposi’s sarcoma-associated herpesvirus, KSHV)，是一种人类γ-2型疱疹病毒。在不同种族和地区人群感染率差异较大。当HHV-8感染免疫功能正常人群时，病毒复制受限、HHV-8-DNA拷贝数较低、仅表达少量潜伏期蛋白，不易被机体免疫监察系统察觉，从而发展为终身潜伏感染。而当HHV-8感染免疫功能紊乱或免疫功能缺陷人群时，可发展为卡波西肉瘤(Kaposi’s sarcoma, KS)、多中心性卡斯特莱曼病(multicenter Castleman’s disease, MCD)、原发性渗出性淋巴瘤(primary effusion lymphoma, PEL)，以及最近报道的KSHV炎性细胞因子综合征(KSHV inflammatory cytokine syndrome, KICS)，其死亡率高达60%。HHV-8主要通过干扰机体固有免疫和适应性免疫信号通路和表达病毒微小核糖核酸(microRNA, miRNA)等途径破坏机体免疫应答，导致其在宿主细胞内终身潜伏甚至发展为恶性肿瘤。本综述旨在探讨HHV-8的免疫逃逸机制，为HHV-8相关恶性肿瘤的免疫治疗及生物标志物提供思路。

Abstract:

Human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV), is a human gamma-2 herpesvirus. The prevalence of HHV-8 infection varies widely among populations of different races and regions. When infecting immunocompetent people, HHV-8 exhibits limited replication, with low HHV-8-DNA copy number, and expresses only a few of latent proteins. Therefore, it is not easy to be detected by the body’s immune surveillance system and develops into a lifelong latent infection. In contrast, when infecting immunocompromised or immunodeficient populations, HHV-8 could lead to Kaposi’s sarcoma, multicenter Castleman’s disease, primary effusion lymphoma, and KSHV inflammatory cytokine syndrome, inducing a mortality rate as high as 60%. HHV-8 disrupts the immune response by interfering with innate and adaptive immune signaling pathways and expressing viral microRNA, resulting in lifelong latency and even the development of malignant tumors. This paper systemically reviewed various immune evasion mechanisms employed by HHV-8, aiming to provide ideas for developing immunotherapy and biomarkers for HHV-8-related malignant tumors.