宿主蛋白ANP32A在H9N2禽流感病毒跨种感染中的作用及其分子机制研究

Avian influenza virus (AIV) mainly infects poultry and wild birds, and can have the potential ability of cross-species transmission to humans and other mammals, which brings a great threat to poultry industry and public health security. The PB2-E627K mutation (PB2/E627K) of AIV is closely related to viral infection and adaptation to mammals. Recent studies showed that host ANP32A protein may be a novel host restriction factor of AIV and be related to viral PB2/E627K mutation, but the specific molecular mechanism is still unclear. Based on this, previous identified H9N2 AIV that have the potential to cross the species of mammalian was used as a model to perform the further study. We firstly will explore the effects of ANP32A on H9N2 AIV replication in mammalian cells and PB2/E627K mutation, then determine the effects of ANP32A on polymerase function of H9N2 AIV, and finally reveal the effects of critical domain of ANP32A on PB2/E627K mutation. This study aims to determine the role of ANP32A in cross-species infections of H9N2 AIV and to reveal the exact molecular mechanism, which laid the important foundation for clarifying cross-species infection mechanism of AIV.

禽流感病毒(Avian influenza virus, AIV)主要感染家禽及野生鸟类,并能跨种间传播给人等哺乳动物,给养禽业和公共卫生安全带来具大威胁。AIV PB2蛋白627位点突变( PB2/E627K)与病毒感染和适应哺乳动物密切相关。研究发现宿主蛋白ANP32A可能与AIV宿主限制性以及病毒PB2/E627K突变有关,但是具体的分子机制尚不清楚。基于此,本项目以前期发现的可跨种感染哺乳动物的H9N2 AIV为研究模型,首先探索ANP32A对H9N2 AIV在哺乳动物细胞复制和发生PB2/E627K突变的影响,进而确定ANP32A对H9N2 AIV聚合酶功能,最后解析ANP32A关键氨基酸区域影响病毒PB2/E627K突变的分子基础,从而确定ANP32A在H9N2 AIV跨种感染中的作用并揭示具体分子机制,为阐明禽流感病毒的跨种感染机制提供重要的理论基础。

禽流感病毒（Avian influenza virus,AIV） PB2蛋白627位点突变( PB2/E627K)与病毒感染和适应哺乳动物密切相关。研究发现宿主蛋白ANP32A可能与AIV宿主限制性以及病毒PB2/E627K突变有关,但是具体的分子机制尚不清楚。基于此,本项目以前期发现的可跨种感染哺乳动物的H9N2 AIV为研究模型,首先探索ANP32A对H9N2 AIV在哺乳动物细胞复制和发生PB2/E627K突变的影响,进而确定ANP32A对H9N2 AIV聚合酶功能活性的影响,通过解析ANP32A关键氨基酸区域影响病毒PB2/E627K突变的分子基础,发现ANP32A影响AIV PB2/E627K突变，确定了ANP32A在H9N2 AIV跨种感染中的作用机制,为阐明禽流感病毒的跨种感染机制提供了重要的理论基础。本研究的发现证实了哺乳动物宿主蛋白ANP32A促使AIV在哺乳动物细胞复制过程中发生PB2/E627K突变，进而增强病毒的复制能力和毒力，也是影响AIV在哺乳动物细胞上复制能力的主要因素之一。通过本研究可以通过改造特定的细胞系，使哺乳动物细胞更有利于禽流感疫苗株的生长和复制，具有较好的应用前景。