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KMID : 1120220110020010015
Osong Public Health and Research Perspectives
2011 Volume.2 No. 1 p.15 ~ p.22
Pathogenesis and Chronologic Localization of the Human Influenza A (H1N1) Virus in Cotton Rats
Kwon Dong-Hyok

Shin Kyeong-Cheol
Shin Jin-Young
Lee Joo-Yeon
Ha Yoon-Cheol
Lee Nam-Joo
Oh Hee-Bok
Chae Chan-Hee
Kang Chun
Abstract
Objectives: We aimed to evaluate the pathogenesis and chronologic localization of human influenza A (H1N1) virus in experimentally infected cotton rats.

Methods: The animals were intranasally inoculated with 107 plaque-forming units of A/Solomon Islands/3/2006 (H1N1) influenza virus and evaluated for pathogenicity for a period of 28 days. Virus replication kinetics and pathological properties were assessed chronologically. Acute antiviral responses were evaluated by mean of real-time polymerase chain reaction.

Results: Cotton rats infected with A/Solomon Islands/3/2006 virus lost weight until 6 days post-inoculation (DPI) and showed decreased activity until 3 DPI. At necropsy, focal areas of redness and consolidation of lungs were evident at 1, 2, and 3 DPI. Lung histopathology showed moderate to severe interstitial pneumonia, alveolitis and bronchiolitis. Influenza A specific viral protein was detected in bronchiolar epithelial cells, alveolar septa and pneumocytes. Influenza viruses were recovered from the lungs during the early period of infection and the titer peaked at 1 DPI. Viral proteins were detected from 4 hours to 6 hours DPI. These trends correlate with the up-regulation of mRNA expression of the IFN-¥á, Mx1, and Mx2 genes that play critical roles in the anti-influenza response at the early stage of infection.

Conclusion: Our results provide evidence that supports the use of cotton rats for the study of influenza virus pathogenesis and the immune response.
KEYWORD
cotton rats, influenza A (H1N1) virus, localization, pathogenesis
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