人源札幌病毒抗原多样性及遗传进化研究进展

Research progress in antigenic diversity and genetic evolution of human sapoviruses

摘要:

人源札幌病毒(human sapovirus, HuSaV)是全球范围内引起散发性急性胃肠炎和相关疫情的重要病原,尤其对婴幼儿及免疫缺陷患者等高危人群存有致死的危险,人源札幌病毒具有丰富的抗原和遗传多样性,其抗原多样性及免疫原性主要位于P2亚结构域,并且衣壳蛋白免疫原性是人源札幌病毒疫苗研发的理论基础。由于人源札幌病毒可以耐受高衣壳突变而不失去病毒功能使它得以迅速进化,其在宿主体内进化过程中存在连续的氨基酸突变,且突变主要在VP1的P结构域内积累,少见于非结构蛋白和VP2中。序列和结构的改变使得人源札幌病毒逃脱先前存在的群体免疫,有必要进一步探索人源札幌病毒的免疫逃逸机制及其拮抗宿主的免疫应答。因此,本文针对人源札幌病毒在基因组特征、抗原多样性特点、遗传进化机制等领域的研究进展进行了系统综述,并对未来研究中亟待解决的科学问题进行了展望。

Abstract:

Human sapoviruses (HuSaV) are major pathogens causing sporadic acute gastroenteritis and related epidemics worldwide, especially in high-risk populations such as infants and immunocompromised patients. With rich antigenic and genetic diversity, human sapoviruses exhibit antigenic diversity and immunogenicity mainly in the P2 subdomain. The immunogenicity of the capsid protein is the theoretical basis for the development of vaccines against the viruses. With strong tolerance to capsid mutations without losing viral function, human sapoviruses can evolve rapidly through continuous amino acid mutations in the host, with mutations accumulating mainly in the P domain of VP1 and rarely in non-structural proteins and VP2. Sequence and structural changes enable human sapoviruses to escape the existing population immunity. Therefore, it is essential to explore the immune escape mechanisms of human sapoviruses and their antagonistic effects on host immune responses. This paper systematically reviews the studies of human sapoviruses in terms of genome characteristics, antigenic diversity characteristics, and genetic evolution mechanism, and puts forward the problems to be solved in the future research.