云南省新型戊型肝炎病毒的分布、感染、进化和致病性研究

We found that there are the genotypes of novel hepatitis E viruses (HEV) in the rodents (Apodemus cheverieri and Eothenomys) in Yunnan Province, China and the genomes of the four strains of HEV have been sequenced. From the phylogenetic tree, there are not only close to the Orthohepevirus C genotype of HEV, but also the other novel HEV in Yunnan Province. There are many genotypes of HEV cycling in the hosts in the same areas. The results showed the phenomenon of virus genetic diversity. HEV causes hepatitis E (HE). HE is zoonosis mainly transmitted by fecal and oral and harbored by domestic or wild animals. HE is not only public health problem in China, but also has become a global concern. The hosts (Apodemus cheverieri and Eothenomys) are the dominant species of rats in the cultivated lands distributed all over the Yunnan Province and their activities are very closely related to production and living of human. So it is necessary to perform a system research on the novel HEV harbored by the hosts (Apodemus cheverieri and Eothenomys). On the basis of previous work, this study makes further investigation on the distribution, infected situation, genetic variation of the novel HEV, and the evolutionary relationships among the HEV and hosts. The study reveals the pathogenicity of the novel HEV to human and rat for providing technical guidance of surveillance, control and prevention of HE in Yunnan Province.

申请人前期在云南省鼠类（高山姬鼠和绒鼠）中发现存在一类新型戊型肝炎病毒(HEV)，并完成了4株HEV全基因组测序。从系统进化树来看，云南省不仅存在与Orthohepevirus C 型接近的HEV，而且也存在其它新型的HEV，说明在同一地区有多型HEV在宿主动物中循环，呈现出病毒遗传多样性的现象。HEV引起的戊型肝炎，是一种主要经粪-口传播，以家畜或野生动物为宿主的人兽共患病。该病已成为我国乃至全球关注的公共卫生问题。高山姬鼠和绒鼠是云南省山间耕地的优势鼠种，分布范围广，与人的关系十分密切，有必要对他们携带的新型HEV进行系统的研究。本研究在前期工作的基础上，进一步调查该新型HEV在云南省的分布、感染现状、遗传变异以及病毒与宿主动物间的进化关系；同时解析该类新型病毒对人和鼠的致病性，为戊型肝炎的监测、预防和控制提供指导。

背景：云南省鼠类（高山姬鼠和绒鼠）中发现存在一类新型戊型肝炎病毒(Hepatitis E Viruses，HEV)，从系统进化树来看，云南省不仅存在与正戊肝病毒C (Orthohepevirus C) 型接近的HEV，而且也存在其它新型的HEV，说明在同一地区有多型HEV在宿主动物中循环，呈现出病毒遗传多样性的现象。高山姬鼠和绒鼠是云南省山间耕地的优势鼠种，分布范围广，与人的关系十分密切，有必要对他们携带的新型HEV进行系统的研究。.研究内容：本研究在前期工作的基础上，进一步调查该新型HEV在云南省的分布、感染现状、遗传变异以及病毒与宿主动物间的进化关系；同时解析该类新型病毒对人和鼠的致病性，为戊型肝炎的监测、预防和控制提供指导。.结果与科学意义：我们确定了该类新型戊型肝炎病毒的分类地位：来自高山姬鼠（Apodemus chevrieri）和黑腹绒鼠（Eothenomys melanogaster）分别命名为：HEV-C3和HEV-C4。在长吻鼩鼱（Sorex araneus）中发现一种新基因型的戊型肝炎病毒，我们拟命名为HEV-A9。云南省只要有高山姬鼠和黑腹绒鼠分布的地区就有HEV-C3和HEV-C4的分布。云南省发现的戊型肝炎病毒与其宿主存在遗传物种多样性，存在HEV-C1、HEV-C2、HEV-C3和HEV-C4，还存在其他新型戊型肝炎病毒，且病毒与宿主存在共进化（Co-evolution）和跨种传播（Cross-species communication）现象。该类新型戊型肝炎病毒对宿主动物有一定的致病性，致病性不明显。该结果可以用于建立戊型肝炎病毒动物模型、病毒分离、疫苗研制和药物筛选，并对戊型肝炎的预防控制有一定的指导意义。