Memoli Matthew J, Tumpey Terrence M, Jagger Brett W, Dugan Vivien G, Sheng Zong-Mei, Qi Li, Kash John C, Taubenberger Jeffery K
Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3203, USA.
Virology. 2009 Oct 25;393(2):338-45. doi: 10.1016/j.virol.2009.08.021. Epub 2009 Sep 5.
The 1918 pandemic influenza virus has demonstrated significant pathogenicity in animal models and is the progenitor of 'classical' swine and modern seasonal human H1N1 lineages. Here we characterize the pathogenicity of an early 'classical' swine H1N1 influenza A virus isolated in 1931 compared to the pathogenicity of the 1918 pandemic virus and a seasonal H1N1 virus in mice and ferrets. A/Swine/Iowa/31 (Sw31) and the 1918 influenza viruses were uniformly lethal in mice at low doses and produced severe lung pathology. In ferrets, Sw31 and 1918 influenza viruses caused severe clinical disease and lung pathology with necrotizing bronchiolitis and alveolitis. The modern H1N1 virus caused little disease in either animal model. These findings revealed that in these models the virulence factors of the 1918 influenza virus are likely preserved in the Sw31 virus and suggest that early swine viruses may be a good surrogate model to study 1918 virulence and pathogenesis.
1918年大流行性流感病毒在动物模型中已显示出显著的致病性,并且是“经典”猪流感病毒株和现代季节性人类H1N1谱系的始祖。在此,我们对1931年分离出的一株早期“经典”猪H1N1甲型流感病毒的致病性进行了表征,并将其与1918年大流行性病毒和一种季节性H1N1病毒在小鼠和雪貂中的致病性进行了比较。A/猪/爱荷华/31(Sw31)和1918年流感病毒在低剂量时对小鼠均具有致死性,并导致严重的肺部病变。在雪貂中,Sw31和1918年流感病毒引起严重的临床疾病和肺部病变,伴有坏死性细支气管炎和肺泡炎。现代H1N1病毒在这两种动物模型中均很少引起疾病。这些发现表明,在这些模型中,1918年流感病毒的毒力因子可能在Sw31病毒中得以保留,这表明早期猪流感病毒可能是研究1918年病毒毒力和发病机制的良好替代模型。