Pathology of human influenza A (H5N1) virus infection in cynomolgus macaques (Macaca fascicularis)

被引:99
作者
Kuiken, T [1 ]
Rimmelzwaan, GF [1 ]
Van Amerongen, G [1 ]
Osterhaus, ADME [1 ]
机构
[1] Erasmus Med Ctr, Natl Influenza Ctr, Inst Virol, NL-3000 DR Rotterdam, Netherlands
关键词
acute respiratory distress syndrome; cynomolgus macaques; immunohistochemistry; influenza A (H5N1) virus; multiple-organ dysfunction syndrome; nonhuman primate model; pathology;
D O I
10.1354/vp.40-3-304
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Infection with influenza A (H5N1) virus, which has not been associated with respiratory disease in humans previously, caused clinical signs of acute respiratory distress syndrome and multiple-organ dysfunction syndrome with high mortality in humans in Hong Kong in 1997. To study the pathogenesis of this disease, we infected four cynomolgus monkeys (Macaca fascicularis) with 2.5 X 10(4) median tissue culture infectious dose (TCID50) of influenza virus A/Hong Kong/156/97 (H5N1) and euthanatized them 4 or 7 days after infection. The main lesion was a necrotizing broncho-interstitial pneumonia (4/4) similar to those found in primary influenza virus pneumonia in humans, with desquamation of respiratory epithelium (4/4), intra-alveolar hemorrhage (4/4), hyaline membrane formation (2/4), and infiltration with neutrophils and macrophages (4/4). Lesions in other organs consisted of a suppurative tonsillitis (2/4) and necrosis in lymphoid organs (1/4), kidney (1/4), and liver (1/4). By immunohistochemistry, influenza virus antigen was limited to pulmonary tissue (4/4) and tonsils (2/4). Based on these results, we suggest that the cynomolgus monkey is a suitable animal model for studying the pathogenesis of human H5N1 virus infection and that multiple-organ dysfunction syndrome in this disease may be caused by diffuse alveolar damage from virus replication in the lungs alone.
引用
收藏
页码:304 / 310
页数:7
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