H5N1亚型禽流感病毒HA糖基化位点对树突状细胞天然免疫的影响及其机制

H5亚型禽流感病毒（AIV）可通过改变血凝素（HA）糖基化位点影响病毒对宿主的致病力及天然免疫水平。在AIV感染过程中，树突状细胞（DCs）除了作为抗原递呈细胞外，也是天然免疫调控的关键。然而HA糖基化位点的改变对DCs天然免疫功能的影响及机理仍不清楚。因此开展如下研究：（1）比较具有致病性差异的不同糖基化位点AIV（野生型、158位缺失、169位缺失重组病毒；反向遗传技术构建）对小鼠/鸡DCs的感染能力；（2）比较各毒株对DCs天然免疫功能的影响，包括DCs吞噬能力、表型、活化、迁移、细胞因子表达、感染DCs刺激T细胞增殖与分化、感染DCs对呼吸道上皮细胞/巨噬细胞/T细胞的感染情况及细胞因子表达水平；（3）阐明唾液酸受体在各毒株诱导DCs天然免疫中的作用；（4）分析糖基化位点的改变对C型凝集素受体识别AIV能力的影响。本研究将为进一步阐明H5N1 AIV的致病机理奠定基础。

Hemagglutinin (HA) glycosylation site change of H5 subtype avian influenza virus (AIV) results in different pathogenicity and innate immune response. During AIV infection, dendritic cells (DCs), as important antigen-presenting cells, play a key role in the regulation of innate immune response. However, the effect and mechanism that different glycosylation sites regulate innate immune function of DCs, remain unclear. In our study, main contents are as follows: (1) Compare the infection ability of rs-AIVs (Wide Type, 158N, and 169N reassortant H5N1 viruses were constructed by reverse genetics technology) on the mice/chicken DCs; (2) Compare the innate immune response levels of DCs induced by rs-AIVs, including phagocytosis, phenotype, activation, migration, cytokines, T lymphocytes proliferation and differentiation by AIV infected-DCs, and the infection and cytokines levels of airway epithelial cells, macrophages, and T lymphocytes by AIV infected-DCs; (3) The effect of sialic acid receptors on the innate immune response of DCs induced by rs-AIVs. (4) The effect of HA glycosylation site change on the recognition of viruses by C-type lectin receptors. Our study will lay the foundation for further clarifying pathogenesis mechanism of H5N1 AIV.