Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus

被引:116
作者
Khatri, Mahesh [1 ]
Dwivedi, Varun [1 ]
Krakowka, Steven [2 ]
Manickam, Cordelia [1 ]
Ali, Ahmed [1 ]
Wang, Leyi [1 ]
Qin, Zhuoming [1 ,3 ]
Renukaradhya, Gourapura J. [1 ,4 ]
Lee, Chang-Won [1 ,4 ]
机构
[1] Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Wooster, OH 44691 USA
[2] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA
[3] Shandong Acad Agr Sci, Inst Poultry Sci, Jinan 250023, Peoples R China
[4] Ohio State Univ, Coll Vet Med, Dept Vet Prevent Med, Columbus, OH 43210 USA
关键词
PORCINE RESPIRATORY CORONAVIRUS; CYTOTOXIC T-LYMPHOCYTE; A VIRUS; HETEROSUBTYPIC IMMUNITY; CYTOKINE RESPONSES; UNITED-STATES; INFECTION; CELLS; PROTECTION; ABSENCE;
D O I
10.1128/JVI.01211-10
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-gamma by lymphocytes of the tracheobronchial lymph nodes was also detected. Higher frequencies of cytotoxic T lymphocytes, gamma delta 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.
引用
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页码:11210 / 11218
页数:9
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