Maeda T, Kawasaki K, Ohnishi S
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4133-7. doi: 10.1073/pnas.78.7.4133.
The molecular mechanism of hemolysis and fusion by influenza virus in acidic media was studied. First, the effect of trypsin treatment on the activity of fibroblast-grown influenza virus was studied. The results showed that the split form of viral hemagglutinin, HA1 and HA2, but not the precursor, is responsible for the activity. Second, the interaction of egg-grown influenza virus, which contains the split hemagglutinin, with lipid liposomes was studied by spin labeling and electron microscopy. Phospholipid transfer from the viral envelope to the lipid bilayer membrane occurred within 30 s at pH 4.5-5.4. The transfer is largely independent of the lipid composition and the crystalline vs. liquid/crystalline state of the membrane. Virus-induced lysis of liposomes also took place rapidly in the same pH range. Envelope fusion with liposomes occurred at pH 5.2 but not at pH 7.0. These characteristic interactions were similar to those between influenza virus and erythrocytes reported previously. On the other hand, hemagglutinating virus of Japan did not interact with liposomes at neutral pH. These results suggest that protonation of the NH2-terminal segment of the HA2 form causes interaction of the segment with the lipid core of the target cell membrane, leading to hemolysis and fusion.
研究了流感病毒在酸性介质中溶血和融合的分子机制。首先，研究了胰蛋白酶处理对成纤维细胞培养的流感病毒活性的影响。结果表明，病毒血凝素的裂解形式HA1和HA2而非前体负责该活性。其次，通过自旋标记和电子显微镜研究了含有裂解血凝素的鸡胚培养流感病毒与脂质体的相互作用。在pH 4.5 - 5.4条件下，磷脂在30秒内从病毒包膜转移至脂质双分子层膜。这种转移很大程度上与脂质组成以及膜的晶态与液晶态无关。在相同pH范围内，病毒诱导的脂质体裂解也迅速发生。包膜与脂质体的融合在pH 5.2时发生，而在pH 7.0时不发生。这些特征性相互作用与先前报道的流感病毒和红细胞之间的相互作用相似。另一方面，日本血凝病毒在中性pH下不与脂质体相互作用。这些结果表明，HA2形式的NH₂末端片段的质子化导致该片段与靶细胞膜的脂质核心相互作用，从而导致溶血和融合。
