H5N1高致病性禽流感传播网络与关键节点研究

Highly pathogenic avian influenza H5N1 and its long-term persistence worldwide have resulted in avian influenza panzootics, public health issues, enormous economic losses, and ecological problems in China. H5N1 viruses have been shown to be transmitted by bird migration, poultry transportation, and bird-poultry interface, which results a complex transmission pattern. On the basis of our previous studies, we propose that H5N1 viruses circulate across fixed networks, and spread through the hubs between transmission networks. To verify this scientific hypothesis, we will create an empirical transmission model at bird-poultry interface based on spatial analysis and bioinformatics, including continuous and discontinuous transmission, to reconstruct spatiotemporal diffusion process by simulating viral gene flow in China. The project is therefore divided into 3 main parts: (1) The relationship between bird migration and H5N1 discontinuous transmission, and poultry transportation and H5N1 continuous transmission in China; (2) Quantify the interrelatedness between bird migration and poultry transportation networks in viral transmission; (3) We will evaluate transmission networks of H5N1 virus and its key hubs to predict risk of human H5N1 infection across regions. Our study will reveal H5N1 viral transmission and geo-spread patterns, and provide the theory basis for effectively preventing the spread of H5N1 and other HPAI virus, especially H5N1 outbreak in humans.

H5N1高致病性禽流感在全球持续流行，对中国公共卫生、经济发展、动物生态产生了巨大破坏。候鸟迁徙、家禽运输、以及候鸟与家禽的交互接触都会感染传播病毒，造成H5N1禽流感的空间扩散与人感染事件错综复杂。结合前期研究，我们提出：H5N1禽流感病毒通过固定传播网络进行空间扩散，地理关联节点促进其进化与跨网络传播。为验证这一假设，我们拟结合空间分析与生物信息学方法，构建中国H5N1禽流感候鸟非连续式、家禽连续式交互传播模型，通过模拟病毒基因流，还原其时空扩散过程。研究内容包括：（1）中国主要候鸟迁徙路线、家禽运输网络与H5N1禽流感非连续、连续传播的关系；（2）量化候鸟迁徙网络与家禽运输网络的交互作用；（3）评估H5N1禽流感传播网络与关键节点，预测出现人感染H5N1禽流感病毒的风险。研究将为认识H5N1禽流感扩散规律，高效开展H5N1及其他亚型高致病性禽流感传播的控制工作提供重要依据。

高致病性禽流感的持续性变异、传播造成其在我国形成大面积流行和局部地区的长时间流行，对我国的家禽产业造成了巨大的打击，并对公共健康产生了极大的威胁。本研究对已有研究做了全面的调查，发现家禽的生产、运输和贸易链与H5N1禽流感的传播风险存在显著关联，但是由于国内家禽运输贸易数据的缺失、传统流行病学研究方法的局限，H5N1高致病性禽流感病毒在我国家禽中传播、进化的时空规律和与家禽贸易运输的关系仍未被掌握。所以本研究着眼于填补这一认识空白，在收集整理中国历年H5N1高致病性禽流感病毒的HA基因序列、家禽生产与运输相关的地理环境条件数据和社会经济统计数据的基础上，综合运用数学建模、空间分析技术、生物信息学等方法，对中国各省间年度的H5N1高致病性禽流感病毒进化和扩散的时空动态进行研究，并取得了以下研究成果：1）明确了中国主要候鸟迁徙路线、家禽运输网络与H5N1禽流感的传播关系；2）确定了H5N1高致病性禽流感病毒的地理分布结构性，发现了以广东为辐射中心，邻近省份间连续传播的模式；3）识别国道运输网络为国内家禽中H5N1高致病性禽流感病毒在各省间传播过程中的关键因素，国道运输网络应为H5N1网络传播的关键节点；4）将H5N1高致病性禽流感病毒研究成果推广应用到其他亚型禽流感病毒，发现H7N9型禽流感在我国出现向西迁移的趋势，陕西各城市H7N9病毒感染来源可能为当地的活禽市场或农场。项目成果为认识H5N1禽流感病毒扩散规律，高效开展H5N1及其他亚型高致病性禽流感传播的控制工作提供了重要依据。