调控肿瘤相关疱疹病毒潜伏及免疫逃逸策略的研究

Human γ-herpesvirus is a tumor-associated virus and is closely related to a variety of tumors like nasopharyngeal carcinoma and Burkitt's lymphoma. It is well known vaccination can prevent the virus-associated tumors. Since the virus could establish latent infection and immune evasion after infection, there is still no effective vaccine against γ-herpesvirus. Furthermore, the regulation of latent infection and immune evasion is not very clear. Our previous study have found that sustained expression of immediate early gene RTA or deletion of latency-associated genes can cause loss of latent infection, while still induce specific cellular and humoral immune responses. In addition, we have found that there exists immune evasion genes which suppress either type I interferon production or signaling pathway activation, and virus could also produce SOCS1 to suppress the anti-viral effect of interferons. Based on the above work, we construct a recombinant virus which is deficient in latent infection and immune evasion and the virus could induce humoral and cellular immune response and does not cause tumors. Studying the biological characteristics of the recombinant virus and the regulation of γ-herpesvirus latency and immune evasion as well as the host immune response will deepen our understanding of the tumorigenesis of γ-herpesvirus and provide a solid foundation for the study of γ-herpesvirus vaccine which could prevent and treat the associated tumors, thereby reducing the tumor incidence.

人类γ疱疹病毒为肿瘤相关病毒，与鼻咽癌、Burkitt’s淋巴瘤等多种肿瘤发生密切相关。疫苗接种可预防病毒相关肿瘤的发生，但由于γ疱疹病毒潜伏感染及免疫逃逸的存在，迄今尚无有效的疫苗问世。本课题组以鼠γ疱疹病毒MHV68为模型，通过前期大量的工作积累表明持续表达病毒即刻早期基因RTA或去除潜伏期相关基因可造成病毒潜伏感染的丧失，并可诱导特异性细胞及体液免疫应答；病毒可通过自身免疫逃逸基因或诱导宿主细胞产生抗干扰素蛋白如SOCS1，抑制I型干扰素产生或功能。本项目将在上述工作基础上展开，通过构建一种潜伏感染免疫逃逸缺失的重组病毒DIP-S，以细胞、动物感染为模型，深入研究该重组病毒体内激发的免疫效应，阐明保护性免疫应答及抗潜伏感染发生的分子机制。本项目研究结果将有助于加深我们对γ-疱疹病毒潜伏机制及免疫逃逸机制的认识，并为γ疱疹病毒疫苗的研制提供坚实的理论基础。

人类γ疱疹病毒为肿瘤相关病毒，与鼻咽癌、Burkitt’s淋巴瘤等多种肿瘤发生密切相关。疫苗接种可预防病毒相关肿瘤的发生，但由于γ疱疹病毒潜伏感染及免疫逃逸的存在，迄今尚无有效的疫苗问世。本课题组以鼠γ疱疹病毒MHV68为模型，通过前期大量的工作积累表明持续表达病毒即刻早期基因RTA或去除潜伏期相关基因可造成病毒潜伏感染的丧失，并可诱导特异性细胞及体液免疫应答；病毒可通过自身免疫逃逸基因或诱导宿主细胞产生抗干扰素蛋白如SOCS1，抑制I型干扰素产生或功能。本项目将在上述工作基础上展开，通过构建一种潜伏感染免疫逃逸缺失的重组病毒DIP-S，以细胞、动物感染为模型，深入研究该重组病毒体内激发的免疫效应，阐明保护性免疫应答及抗潜伏感染发生的分子机制。本项目研究结果将有助于加深我们对γ-疱疹病毒潜伏机制及免疫逃逸机制的认识，并为γ疱疹病毒疫苗的研制提供坚实的理论基础。