导致季节性流感流行的氨基酸变异形式研究

项目名称： 导致季节性流感流行的氨基酸变异形式研究

项目编号： No.81473035

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王海天

作者单位： 香港中文大学深圳研究院

项目金额： 70万元

中文摘要： 季节性流感为现今社会公共卫生带来很大的负担，并且对人民健康有重大的威胁。了解流感流行背后病毒快速变异和导致新亚型流行的机制对流感的预防及应对有着至关重要的作用。此前流感流行研究主要用血清学的方法报告人群中的流行情况，以及从流感病毒基因的角度分析与过往亚型的分别。我们提出可以结合这两种研究类型的新方法。我们前期研究中发现流感亚型病毒HA上多个氨基酸同时变异与该亚型的血清抗体浓度有着清晰的关联，我们提出这种变异形式的发生导致流感流行的假设，并旨在此项目中收集更多数据验证这个假设，并基于氨基酸变异的形式提出数学模型以预测未来此种变异形式发生的时间。本项目提出的方法有助于预测来年流感流行的亚型以及发生时间，并为疫苗研发提供重要靶点。

中文关键词： 流感病毒；基因突变

英文摘要： Influenza epidemics have been a major source of local hospitalization and impose an enormous burden to public health care. Understanding their cause is crucial for the creation of intervention strategies and early preventions. Previous studies on influenza epidemics concentrate mainly into two areas: serological data reflecting epidemiological characteristics, and phylogenic methods using genetic sequences to analyze viral evolution. There are few overlaps between the two types of studies, although information from both sides is indispensible towards revealing the role of viral evolution in influenza epidemics. In the proposed study, we aim to bridge the gap by associating the pattern of antigenic drifts to a significant seasonal influenza A/H3N2 epidemic in 2011. In our preliminary study using hemagglutinin segment sequences, we found a clear association of hemagglutinin inhibition peak corresponding to simultaneous antigenic drifts. This theory is also demonstrated to work on 2009 H1N1 and influenza type B. We propose to test the phenomenon on neuraminidase segment sequences of existing subjects, and test on future subjects for a longer period of time. We will also develop mathematical models based on the observed phenomenon using hidden Markov chain and stochastic processes. A prediction of future influenza epidemics might then be possible. Our study will offer key knowledge on the genetic source underlying influenza epidemics, the amino acids positions identified can serve as potential vaccine targets, and the models developed will provide timely information for policy makers for early alerts and for the preparation of next wave seasonal influenza activities.

英文关键词： Influenza;amino acids mutations