WERNER G H, SCHLESINGER R W
J Exp Med. 1954 Aug 1;100(2):203-16. doi: 10.1084/jem.100.2.203.
Electron microscopic study has revealed the morphological entity responsible for the rise in viral hemagglutinin observed in brains of mice after intracerebral inoculation of non-neurotropic strains of influenza virus. This rise in hemagglutinin, although dependent on inoculation of fully infectious virus, is not associated with an increase in infectious titer. The hemagglutinating principle is functionally similar to the "incomplete" influenza virus which can be obtained from chick embryos by serial egg-to-egg transfer of undiluted, infected allantoic fluid according to the method of von Magnus. A method has been described which facilitates selective adsorption of viral particles recovered from organ extracts on saponine-lysed ghosts of fowl erythrocytes. This procedure has been utilized in studying the morphology of non-infectious, hemagglutinating virus from chorio-allantoic membranes or mouse brains and in comparing these two forms with each other and with ordinary, infectious (standard) influenza virus. Standard virus isolated from allantoic fluids or membranes of infected eggs was found to contain uniform particles of predominantly spherical shape with smooth surface and even density, resembling those described by others. The appearance of such particles was not affected by the procedure of extraction and concentration used. In contrast, non-infectious, hemagglutinating virus obtained either from allantoic sacs ("undiluted passages") or from mouse brain was pleomorphic and seemed to consist of disintegrating particles. The majority appeared flattened and bag-like and had a rough, granular surface and reduced, uneven density. 37 per cent of the non-infectious particles isolated from mouse brain infected with the non-neurotropic strain WS had diameters in excess of 170 mmicro, as compared with only 2 per cent of the particles of the parent strain itself. Regardless of whether or not the contrast in appearance of standard and of non-infectious particles was due to differing resistance to the preparatory treatment, it indicated the existence of basic structural differences between the two types of virus. Correlation of particle counts with hemagglutinin titers has shown that the non-infectious virus obtained from mouse brain is, unit for unit, an equivalent counterpart of standard virus derived from infected eggs. The end-point of hemagglutination in a pattern test corresponds for both forms to that dilution at which the ratio virus particles/red cells approaches one. The quantitative data based on particle counts support the assumption that non-infectious virus arises in mouse brain as a product of viral multiplication.
电子显微镜研究揭示了在脑内接种非嗜神经株流感病毒的小鼠脑中观察到的病毒血凝素升高的形态学实体。血凝素的这种升高虽然依赖于接种完全感染性病毒，但与感染滴度的增加无关。血凝原理在功能上类似于“不完全”流感病毒，这种病毒可根据冯·马格努斯的方法，通过将未稀释的感染尿囊液在鸡胚之间连续传代获得。已经描述了一种方法，该方法有助于从器官提取物中回收的病毒颗粒选择性吸附在禽红细胞皂素裂解的空壳上。该程序已用于研究从绒毛尿囊膜或小鼠脑中获得的非感染性血凝病毒的形态，并将这两种形式相互比较以及与普通感染性（标准）流感病毒进行比较。从感染鸡蛋的尿囊液或膜中分离出的标准病毒被发现含有均匀的颗粒，主要为球形，表面光滑，密度均匀，与其他人描述的相似。这种颗粒的外观不受所用提取和浓缩程序的影响。相比之下，从尿囊囊（“未稀释传代”）或小鼠脑中获得的非感染性血凝病毒是多形的，似乎由正在解体的颗粒组成。大多数看起来扁平且呈袋状，表面粗糙、有颗粒，密度降低且不均匀。从感染非嗜神经株WS的小鼠脑中分离出的非感染性颗粒中，3７%的直径超过170微米，而亲本株本身的颗粒中只有2%超过该直径。无论标准颗粒和非感染性颗粒外观上的差异是否归因于对制备处理的不同抗性，这都表明这两种病毒在基本结构上存在差异。颗粒计数与血凝素滴度的相关性表明，从小鼠脑中获得的非感染性病毒，单位与从感染鸡蛋中获得的标准病毒相当。在模式试验中，两种形式的血凝终点都对应于病毒颗粒/红细胞比率接近1的稀释度。基于颗粒计数的定量数据支持这样的假设，即非感染性病毒在小鼠脑中作为病毒增殖产物产生。
