戊型肝炎病毒分泌型衣壳蛋白的结构与功能探究

戊型肝炎病毒(HEV)是全球范围内急性病毒性肝炎的最主要诱因之一，在高危人群中（孕妇、老年人和慢性肝病患者）死亡率可高达20~30﹪。流行病毒学研究结果显示虽然高龄人群中HEV血清阳性率较高，但老年人依然为戊肝的易感人群，表明HEV存在免疫逃逸机制。本课题组发现HEV在复制过程中会产生一种分泌型蛋白pORF2S，该蛋白与HEV衣壳蛋白pORF2C同源，但存在完全不同的表达途径且不参与病毒组装。本课题组结合前期研究结果及部分临床报道，发现pORF2S可能在HEV免疫逃逸、重复感染及慢性化过程中起重要作用。因此本课题拟通过对pORF2S进行结构解析，鉴定其关键性表位，并对比与衣壳蛋白pORF2C的异同，通过体内外模型深入研究pORF2S的潜在功能，阐明pORF2S在病毒感染及机体抗体应答过程中的作用，揭示pORF2S与HEV免疫逃逸的相关性，为HEV在免疫力低下人群中的预防与治疗提供理论依据。

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis in the worldwide. The mortality rate can reach as high as 20-30% in high-risk population, such as pregnant women, the elderly and patients with chronic liver disease. The epidemiological studies showed that, although the positive rate of HEV seroprevalence was higher in the elderly, the elderly were still susceptible to hepatitis E. It indicated an immune escape mechanism presented in HEV infection. We found that HEV produced a secreted protein pORF2S during replication, which is homologous to the HEV capsid protein pORF2C. The pORF2S but has an individual expression pathway and does not participate in construction of virions. Based on previous research results and clinical reports, we found that pORF2S may play an important role in the HEV immune escape, reinfection and chronicity. Therefore, this project intends to elucidate the role of pORF2S in viral infection and host antibody responses by analyzing the structure of pORF2S, identifying its key epitopes and comparing it with capsid protein pORF2C, and studying the function of pORF2S in vitro and vivo models. By trying to reveal the relationship between the pORF2S and HEV immune escape, we attempt to provide a theoretical basis for the prevention and treatment of HEV in immunocompromised populations.