Food Animal Health Research Program, Ohio Agricultural Research and Development Center, the Ohio State University, 1680 Madison Avenue, Wooster, OH 44691, USA.
J Virol. 2010 Nov;84(21):11210-8. doi: 10.1128/JVI.01211-10. Epub 2010 Aug 18.
Pigs are capable of generating reassortant influenza viruses of pandemic potential, as both the avian and mammalian influenza viruses can infect pig epithelial cells in the respiratory tract. The source of the current influenza pandemic is H1N1 influenza A virus, possibly of swine origin. This study was conducted to understand better the pathogenesis of H1N1 influenza virus and associated host mucosal immune responses during acute infection in humans. Therefore, we chose a H1N1 swine influenza virus, Sw/OH/24366/07 (SwIV), which has a history of transmission to humans. Clinically, inoculated pigs had nasal discharge and fever and shed virus through nasal secretions. Like pandemic H1N1, SwIV also replicated extensively in both the upper and lower respiratory tracts, and lung lesions were typical of H1N1 infection. We detected innate, proinflammatory, Th1, Th2, and Th3 cytokines, as well as SwIV-specific IgA antibody in lungs of the virus-inoculated pigs. Production of IFN-γ by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, γδ T cells, dendritic cells, activated T cells, and CD4+ and CD8+ T cells were detected in SwIV-infected pig lungs. Concomitantly, higher frequencies of the immunosuppressive T regulatory cells were also detected in the virus-infected pig lungs. The findings of this study have relevance to pathogenesis of the pandemic H1N1 influenza virus in humans; thus, pigs may serve as a useful animal model to design and test effective mucosal vaccines and therapeutics against influenza virus.
猪能够产生具有大流行潜力的重配流感病毒，因为禽流感病毒和哺乳动物流感病毒都可以感染猪呼吸道的上皮细胞。目前流感大流行的源头是 H1N1 甲型流感病毒，可能源自猪。本研究旨在更好地了解 H1N1 流感病毒在人类急性感染期间的发病机制和相关的宿主黏膜免疫反应。因此，我们选择了一种具有感染人类历史的 H1N1 猪流感病毒，Sw/OH/24366/07（SwIV）。临床感染猪出现鼻漏和发热，并通过鼻分泌物排出病毒。与大流行的 H1N1 病毒一样，SwIV 也在上呼吸道和下呼吸道广泛复制，肺部病变是典型的 H1N1 感染。我们在感染病毒的猪肺部检测到固有、促炎、Th1、Th2 和 Th3 细胞因子，以及 SwIV 特异性 IgA 抗体。还检测到气管支气管淋巴结淋巴细胞产生 IFN-γ。在 SwIV 感染猪的肺部，检测到更高频率的细胞毒性 T 淋巴细胞、γδ T 细胞、树突状细胞、活化 T 细胞以及 CD4+和 CD8+T 细胞。同时，在感染病毒的猪肺部也检测到更高频率的免疫抑制性 T 调节细胞。本研究的发现与人类大流行 H1N1 流感病毒的发病机制有关；因此，猪可能是设计和测试针对流感病毒的有效黏膜疫苗和治疗方法的有用动物模型。
