Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Braunschweig, Germany.
Virology. 2011 Mar 30;412(1):36-45. doi: 10.1016/j.virol.2010.12.047. Epub 2011 Jan 22.
Experimental mouse models were used to compare virulence and reproduction rate of three mouse-adapted variants of the PR8 influenza A virus strain. We observed large differences in pathogenicity in two mouse strains. The PR8M variant was lethal in DBA/2J mice but not in C57BL/6J mice, whereas PR8F and hvPR8 variants were lethal in both mouse strains. High lethality of PR8M in DBA/2J correlated with high viral load at early time points after infection and spread of the virus into alveolar regions. Also, higher viral loads and mortality in mice infected with PR8F resulted in a higher number of infiltrating leukocytes. 3D-protein structure predictions of the HA indicated amino acid sequence alterations which may render the HA cleavage site in PR8F more accessible to host proteases. Infection of C57BL/6J mice with a re-assorted PR8 virus revealed that the HA gene is the main determinant of virulence of the PR8F variant.
我们使用实验鼠模型比较了三种适应鼠类的 PR8 流感病毒株的毒力和繁殖率。我们在两种小鼠品系中观察到了致病性的巨大差异。PR8M 变体在 DBA/2J 小鼠中是致死性的，但在 C57BL/6J 小鼠中不是，而 PR8F 和 hvPR8 变体在两种小鼠品系中都是致死性的。PR8M 在 DBA/2J 中的高致死性与感染后早期病毒载量高以及病毒扩散到肺泡区域有关。同样，感染 PR8F 的小鼠中更高的病毒载量和死亡率导致了更多浸润的白细胞。HA 的 3D 蛋白结构预测表明氨基酸序列的改变可能使 PR8F 中的 HA 裂解位点更容易被宿主蛋白酶切割。用重新组装的 PR8 病毒感染 C57BL/6J 小鼠表明，HA 基因是 PR8F 变体毒力的主要决定因素。
