Department of Virology, Erasmus Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Vet Pathol. 2010 Nov;47(6):1040-7. doi: 10.1177/0300985810374836. Epub 2010 Jul 20.
The pathogenesis of lower respiratory tract disease from the pandemic 2009 H1N1 (H1N1v) influenza A virus is poorly understood. Therefore, either H1N1v virus or a seasonal human H1N1 influenza A virus was inoculated into cynomolgus macaques as a nonhuman primate model of influenza pneumonia, and virological, pathological, and microarray analyses were performed. Macaques in the H1N1v group had virus-associated diffuse alveolar damage involving both type I and type II alveolar epithelial cells and affecting an average of 16% of the lung area. In comparison, macaques in the seasonal H1N1 group had milder pulmonary lesions. H1N1v virus tended to be reisolated from more locations in the respiratory tract and at higher titers than seasonal H1N1 virus. In contrast, differential expression of messenger RNA transcripts between H1N1v and seasonal H1N1 groups did not show significant differences. The most upregulated genes in H1N1v lung samples with lesions belonged to the innate immune response and proinflammatory pathways and correlated with histopathological results. Our results demonstrate that the H1N1v virus infects alveolar epithelial cells and causes diffuse alveolar damage in a nonhuman primate model. Its higher pathogenicity compared with a seasonal H1N1 virus may be explained in part by higher replication in the lower respiratory tract.
大流行 2009 年 H1N1（H1N1v）流感 A 病毒引起的下呼吸道疾病的发病机制尚不清楚。因此，我们用人感染季节性 H1N1 流感 A 病毒或 H1N1v 病毒对食蟹猴进行接种，建立流感肺炎的非人灵长类动物模型，并进行病毒学、病理学和微阵列分析。H1N1v 组的猴存在与病毒相关的弥漫性肺泡损伤，累及 I 型和 II 型肺泡上皮细胞，平均影响肺面积的 16%。相比之下，季节性 H1N1 组的猴肺部病变较轻。H1N1v 病毒比季节性 H1N1 病毒更倾向于从呼吸道的更多部位和更高滴度被重新分离出来。相比之下，H1N1v 和季节性 H1N1 组之间信使 RNA 转录本的差异表达没有显示出显著差异。具有病变的 H1N1v 肺样本中上调最明显的基因属于先天免疫反应和促炎途径，与组织病理学结果相关。我们的结果表明，H1N1v 病毒感染肺泡上皮细胞，并在非人灵长类动物模型中引起弥漫性肺泡损伤。与季节性 H1N1 病毒相比，其更高的致病性可能部分归因于下呼吸道的更高复制。
