Preparation From Human Red Cells of a Substance Inhibiting Virus Hemagglutination

Abstract

Experiments on the inhibiting effect of hunian and sheep red blood cell extracts on the hemagglutinating action of mumps and influenza viruses have been described in a previous report (1). Results were presented which suggested that the inhibiting agent found in these red cell extracts was a derivative of, or identical with, the material which in the intact cell constitutes the receptor site for the virus in the hemagglutination reaction. These results consisted partly in a demonstration that, in the systems studied, the species specificity of the inhibition reaction paralleled that of the hemagglutination reaction. Thus it is known that influenza (PR8) virus will agglutinate human and chicken red cells, but not sheep cells; and that mumps virus will agglutinate all three types of red cells. It was found that the human red cell extracts inhibited the agglutination of human and chicken cells by influenza virus; and that of human, chicken, and sheep red cells by mumps virus. Extracts of sheep ceils, however, inhibited the agglutination of sheep cells by mumps virus, but did not inhibit agglutination of human and chicken cells by influenza virus. Further support for the view above mentioned was provided by the discovery that in a mixture of virus and inhibitor at 37°C. the latter was inactivated, just as is the receptor of intact cells under similar conditions in the elution phenomenon described by Hirst (2).Recently three other laboratories have reported interesting data in relation to the effect of various tissue and cell extracts and other substances on virus hemagglutination and multiplication. Friedewald, Miller, and Whafley (3) described the hemagglutination-inhibiting effects of saline extracts of various human and animal tissues and red cells. HorsfaU and McCarty (4) produced evidence to show that certain bacterial and plant polysaccharides seem capable of interrupting the multiplication of PVM virus in mouse lung. The intrapulmonary multiplication of virus was reflected by a rise in hemagglutination titer of triturated infected mouse lung. Administration of the polysaccharides diminished or prevented this increase in titer after infection. Green and Woolley (5) have demonstrated the inhibitory effect of various animal and * Aided by a grant from the National Foundation for Infantile Paralysis.

Enzymatic and Nonenzymatic Alterations of Erythrocyte Surface Antigens

“…On the basis of Hirst's (60) concepts, DeBurgh et al (34) first isolated an acid-labile, influenza virus-inhibiting, ether-soluble substance from human erythrocytes. This material was found in the above-mentioned elinin fraction.…”

Viruses 1950. Proceedings of a conference on the similarities and dissimilarities between viruses attacking animals, plants, and bacteria, respectively. Held at the California Institute of Technology, Mar. 20-22, 1950 ...

“…The fact that irradiated virus remains elutable from red cells suggests that it is capable of destrojdng the red cell receptors. Since many similarities exist between these receptors on red cells and hemagglutinin-inhibitory (VHI) substances extractable from erythrocytes (Friedewald et al, 1947, deBurgh et al, 1948, normal serum (Francis 1947) and various fluids and tissues of susceptible species (Friedewald et al, 1947, Svedmyr i948a,b, Hardy and Horsfall 1948, Schlesinger 1949b, it may be assumed that these inhibitors are cellular receptors in solution. Active influenza virus is capable of destroying these substances in vitro and also in the infected host, and it is likely, in view of its elutability, that irradiated virus can do the same.…”