인플루엔자 바이러스 병인론 연구를 위한 Cotton Rat 모델 개발

초록

Purpose : Influenza viruses cause significant morbidity and mortality in winter season worldwide. It is needed to establish small-animal model to evaluate host immune response easily for the development of effective vaccine and antivirals for the preparedness of influenza pandemic. To study the pathogenesis of human influenza virus, we used cotton rat(Sigmodon hispidus) which is known to be infected naturally by influenza virus. Methods : Animals were infected with influenza A/Wisconsin/67/2005(H3N2) virus, 2006-2007 vaccine strain, intranasally by the application of 0.1 ㎖ virus solution per 100g body weight. Body temperature and weight, viral titers, serum antibody levels, and pathology of the lungs were evaluated during 21 days. Results : It was shown that influenza virus infected cotton rats accompanied by weight loss and decreased temperature. The serum antibody titer rose after 14 dpi(days post inoculation) significantly. Virus replication peaked within 24 h in the lung and decreased after 1 dpi and cleared by day 3. Pulmonary histopathology included early bronchiolar epithelial cell damage, followed by extensive alveolar and interstitial pneumonia with neutrophils and lymphocytes infiltration, and persisted by 6 days. Especially interstitial pneumonia persisted for nearly 21 days. Conclusion : Influenza virus was replicated in the lungs of cotton rat, and infected cotton rat showed clinical signs and pathological lung lesions. These results indicated that cotton rats could be useful for further studies of pathogenesis of respiratory virus including influenza virus.

키워드