Job Emma R, Pizzolla Angela, Nebl Thomas, Short Kirsty R, Deng Yi-Mo, Carolan Louise, Laurie Karen L, Brooks Andrew G, Reading Patrick C
Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Virology. 2016 Jul;494:143-57. doi: 10.1016/j.virol.2016.01.024. Epub 2016 Apr 26.
Many insights regarding the pathogenesis of human influenza A virus (IAV) infections have come from studies in mice and ferrets. Surfactant protein (SP)-D is the major neutralizing inhibitor of IAV in mouse airway fluids and SP-D-resistant IAV mutants show enhanced virus replication and virulence in mice. Herein, we demonstrate that sialylated glycoproteins, rather than SP-D, represent the major neutralizing inhibitors against H3 subtype viruses in airway fluids from naïve ferrets. Moreover, while resistance to neutralizing inhibitors is a critical factor in modulating virus replication and disease in the mouse model, it does not appear to be so in the ferret model, as H3 mutants resistant to either SP-D or sialylated glycoproteins in ferret airway fluids did not show enhanced virulence in ferrets. These data have important implications for our understanding of pathogenesis and immunity to human IAV infections in these two widely used animal models of infection.
关于人类甲型流感病毒（IAV）感染发病机制的许多见解都来自对小鼠和雪貂的研究。表面活性蛋白（SP）-D是小鼠气道液中IAV的主要中和抑制剂，对SP-D耐药的IAV突变体在小鼠中显示出增强的病毒复制和毒力。在此，我们证明唾液酸化糖蛋白而非SP-D是未接触过病毒的雪貂气道液中针对H3亚型病毒的主要中和抑制剂。此外，虽然对中和抑制剂的耐药性是调节小鼠模型中病毒复制和疾病的关键因素，但在雪貂模型中似乎并非如此，因为对雪貂气道液中SP-D或唾液酸化糖蛋白耐药的H3突变体在雪貂中并未显示出增强的毒力。这些数据对于我们理解这两种广泛使用的感染动物模型中人类IAV感染的发病机制和免疫具有重要意义。
