Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
J Virol. 2010 May;84(9):4194-203. doi: 10.1128/JVI.02742-09. Epub 2010 Feb 24.
The pandemic H1N1 virus of 2009 (2009 H1N1) continues to cause illness worldwide, primarily in younger age groups. To better understand the pathogenesis of these viruses in mammals, we used a mouse model to evaluate the relative virulence of selected 2009 H1N1 viruses and compared them to a representative human triple-reassortant swine influenza virus that has circulated in pigs in the United States for over a decade preceding the current pandemic. Additional comparisons were made with the reconstructed 1918 virus, a 1976 H1N1 swine influenza virus, and a highly pathogenic H5N1 virus. Mice were inoculated intranasally with each virus and monitored for morbidity, mortality, viral replication, hemostatic parameters, cytokine production, and lung histology. All 2009 H1N1 viruses replicated efficiently in the lungs of mice and possessed a high degree of infectivity but did not cause lethal disease or exhibit extrapulmonary virus spread. Transient weight loss, lymphopenia, and proinflammatory cytokine and chemokine production were present following 2009 H1N1 virus infection, but these levels were generally muted compared with a triple-reassortant swine virus and the 1918 virus. 2009 H1N1 viruses isolated from fatal cases did not demonstrate enhanced virulence in this model compared with isolates from mild human cases. Histologically, infection with the 2009 viruses resulted in lesions in the lung varying from mild to moderate bronchiolitis with occasional necrosis of bronchiolar epithelium and mild to moderate peribronchiolar alveolitis. Taken together, these studies demonstrate that the 2009 H1N1 viruses exhibited mild to moderate virulence in mice compared with highly pathogenic viruses.
2009 年大流行的 H1N1 病毒（2009 H1N1）仍在全球范围内引起疾病，主要发生在年轻人群中。为了更好地了解这些病毒在哺乳动物中的发病机制，我们使用了一种小鼠模型来评估选定的 2009 H1N1 病毒的相对毒力，并将其与一种在美国流行的代表性三重组人源猪流感病毒进行了比较，这种病毒在当前大流行之前的十多年里一直在猪群中传播。还与重建的 1918 病毒、1976 年 H1N1 猪流感病毒和高致病性 H5N1 病毒进行了比较。用每种病毒通过鼻腔接种小鼠，并监测其发病率、死亡率、病毒复制、止血参数、细胞因子产生和肺组织学变化。所有 2009 H1N1 病毒均在小鼠肺部高效复制，具有高度传染性，但不会引起致命疾病或表现出肺外病毒传播。2009 H1N1 病毒感染后会出现短暂的体重减轻、淋巴细胞减少以及促炎细胞因子和趋化因子的产生，但与三重组猪流感病毒和 1918 病毒相比，这些水平通常较低。与从轻度人类病例中分离的病毒相比，从致命病例中分离的 2009 H1N1 病毒在该模型中并未显示出增强的毒力。组织学上，2009 病毒感染导致肺部病变从轻度至中度细支气管炎，偶尔出现细支气管上皮坏死和轻度至中度细支气管周围肺泡炎。总之，这些研究表明，与高致病性病毒相比，2009 H1N1 病毒在小鼠中表现出轻度至中度毒力。
