Innate immunity to swine influenza virus in its natural host

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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.