Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Virology. 2011 Apr 10;412(2):426-34. doi: 10.1016/j.virol.2011.01.029. Epub 2011 Feb 18.
Pandemic influenza viral infections have been associated with viral pneumonia. Chimeric influenza viruses with the hemagglutinin segment of the 1918, 1957, 1968, or 2009 pandemic influenza viruses in the context of a seasonal H1N1 influenza genome were constructed to analyze the role of hemagglutinin (HA) in pathogenesis and cell tropism in a mouse model. We also explored whether there was an association between the ability of lung surfactant protein D (SP-D) to bind to the HA and the ability of the corresponding chimeric virus to infect bronchiolar and alveolar epithelial cells of the lower respiratory tract. Viruses expressing the hemagglutinin of pandemic viruses were associated with significant pathology in the lower respiratory tract, including acute inflammation, and showed low binding activity for SP-D. In contrast, the virus expressing the HA of a seasonal influenza strain induced only mild disease with little lung pathology in infected mice and exhibited strong in vitro binding to SP-D.
流感大流行病毒感染与病毒性肺炎有关。嵌合流感病毒的血凝素（HA）片段来自于 1918 年、1957 年、1968 年或 2009 年大流行流感病毒，而其基质蛋白（MP）和核蛋白（NP）则来源于季节性 H1N1 流感病毒，构建这些嵌合病毒的目的是分析血凝素在发病机制和细胞嗜性方面的作用，该研究采用的模型为小鼠模型。我们还探讨了肺表面活性蛋白 D（SP-D）与 HA 结合的能力与相应嵌合病毒感染下呼吸道细支气管和肺泡上皮细胞的能力之间是否存在关联。表达大流行病毒血凝素的病毒与下呼吸道的显著病理学有关，包括急性炎症，并表现出对 SP-D 的低结合活性。相比之下，表达季节性流感株血凝素的病毒仅在感染的小鼠中引起轻度疾病和很少的肺部病理学，并在体外表现出对 SP-D 的强结合活性。
