H9N2亚型禽流感病毒基因变异对病毒生物学特性的影响机制

H9N2亚型禽流感病毒（AIV）不但给养禽业造成了严重损失，而且该病毒近期还易与其他亚型禽流感病毒重配而形成新型病毒，如H7N9等。我们前期研究发现，作为新型病毒基因供体的H9N2 AIV均属一个新的基因型，而且该基因型较其他基因型病毒在鸡中的复制水平、排毒时间和传播能力均增强。然而，病毒出现这些新特性的分子机制尚不清楚。本项目拟对我国近年来H9N2亚型AIV基因组进行系统分析，阐明病毒的分子演化规律；利用动物模型比较不同进化分支或基因型H9N2 AIV生物学特性的差异；进而研究相关蛋白基因的变异对病毒生物学特性影响机制，揭示当前优势流行H9N2病毒M基因和PB2基因协同进化以及病毒基因包装信号区变异在新型病毒产生中的作用。为阐明H9N2 AIV成为新型病毒基因供体的机制提供理论依据，并为新型流感病毒的预警提供理论支持，对我国动物流感及人间流感的防控具有意义。

H9N2 subtype avian influenza virus (AIV) caused great economic losses to poultry industry and recently was found to donate its internal genes to generate novel variants, resulting in human fatalities, such as H7N9 and H10N8 viruses. Besides, H9N2 also contributed its gene segments to H5N2 AIV currently circulating in poultry. Our primary findings showed that all the H9N2 AIV providing genes to novel influenza viruses were recognized as a novel genotype. The replication property, viral shedding, and transmissibility of this genotype were enhanced compared with other H9N2 genotypes. However, the molecular mechanism of such biological feature was still unknown. In the proposal, we will systematically analyze the genomes of H9N2 AIVs isolated during recent years and comparatively examine the biological characteristics of H9N2 AIVs from different sublineages or genotypes using animal models. The effect of protein variations on H9N2 AIV biological characteristics will be investigated, and the role of coevolution of M and PB2 genes and packaging signals variation in emerging of novel reassortant influenza viruses will be illustrated. Taken together, the outcome generated from this project will provide valuable information for influenza control and prevention both for animal and human.