Innate immunity to swine influenza virus in its natural host

猪流感病毒（Swine Influenza Virus，SIV）是引起猪流感（Swine Influenza）的病原体，是一种高度传染性的急性病毒性疾病。SIV引起急性呼吸道感染和肺部病变，由于身体状况下降和达到市场重量所需天数增加而造成经济损失。 先天免疫是机体抵抗微生物病原体（包括病毒病原体）的第一道防线。富含亮氨酸重复序列的核苷酸结合结构域分子（NLR）是识别病原体内存在的病原体相关分子模式的三种传感器之一。关于NLR在感测流感病毒在其天然宿主中的感染中的作用知之甚少。本研究拟利用SIV的天然宿主猪，研究NLR和炎性小体在控制SIV感染中的作用。这项建议的长远目标是剖析猪只感染流感病毒后的宿主先天免疫反应。具体而言，我们将研究NLRP 3炎性体在介导对流感病毒感染的应答中的功能。我们推测炎性体信号通路在SIV感染过程中被激活，并在猪抗SIV感染中起重要作用。我们将通过以下具体目标来检验我们的假设：1）。SIV感染后猪中炎性细胞因子表达和肺病理学的表征。2）。猪上皮细胞、巨噬细胞和树突状细胞中炎性小体通路激活的表征。3）。流感病毒感染后炎性小体激活机制的研究。 了解天然宿主对SIV感染的先天免疫反应，特异性靶向NLRP 3炎性体途径以增强功能，可能成为对抗流感病毒感染的新治疗工具。

Swine influenza virus (SIV) is the causative pathogen for swine influenza, a highly contagious, acute viral disease of swine. SIV induces an acute respiratory tract infection and lung lesions, causing economic losses due to decreased body condition and an increase in the number of days needed to reach market weight. The innate immunity is the first line of the host to fight against microbial pathogens, including viral pathogens. The nucleotide-binding domain-leucine-rich repeat-containing molecule (NLR) is one of the three sensors that recognize pathogen-associated molecular patterns presented within the pathogens. Little is known about the role of NLRs in sensing influenza virus infection in its natural host. In this proposal, we will utilize pigs, the natural host of SIV, to study the role of NLR and inflammasome in controlling SIV infection. The long term objective of this proposal is to dissect the host innate immune responses upon influenza virus infection in pigs. Specifically, we will study the function of the NLRP3 inflammasome in mediating response to influenza virus infection. We hypothesize that inflammasome signaling pathway is activated during SIV infection and it plays an important role in protection against SIV infection in pigs. We will test our hypothesis with the following specific aims: 1). Characterization of inflammatory cytokine expression and lung pathology in pigs after SIV infection. 2). Characterization of inflammasome pathway activation in porcine epithelial cells, macrophages and dendritic cells. 3). Investigation of the mechanism by which inflammasome is activated in response to influenza virus infection. Understanding the innate immune responses to SIV infection in its natural host, specifically targeting the NLRP3 inflammasome pathway for enhanced function may become a novel therapeutic tool to combat influenza virus infection.