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  • Author: A. P. Waterson x
  • Organic Chemistry x
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The events leading to the recognition of serum hepatitis (“homologous serum jaundice”) as a disease entity are described and reasons given why seroprophylaxis against measles played an important role in this discovery. The injection of human serum as a prophylactic was practised on an increasing scale from about 1920 to about 1950, by which time it had largely been superseded by immunoglobulin (gamma globulin). Apart from the transfusion of blood and blood products the other major human to human transfer of material was vaccination against yellow fever in the years 1937 - 1940. The consequences of this large scale interchange between human subjects included the dissemination of serum hepatitis virus, and the possibility of transfer of other viruses is discussed.

Eight strains of Newcastle disease virus (NDV) have been examined using the technique of negative contrast electron microscopy, before and after treatment with ether. There is considerable variation in the shape and size of particles in any one strain, and the degree of this pleomorphism varies from strain to strain. The two common features of all the strains are the internal ribonucleoprotein and the rosette-like haemagglutinin formed by disruption of the coat with ether. The effect of ether is to disrupt the particles, but the ease of disruption varies from strain to strain. The products of ether treatment are the internal ribonucleoprotein and the haemagglutinin, which consists of portions of the outer coat. Besides these, the coat itself may in some strains appear almost intact, but stripped of its projections, after ether treatment. With the strains whose pathogenicity was known it has not proved possible to relate structure to degree of pathogenicity.

Fowl plague (KP) virus and virus N have been examined in the electron microscope as both metal shadowed and negatively stained preparations. The particles of KP virus are very similar to those of influenza A. The products of ether splitting are (1) the G antigen, a ribonucleoprotein whose helically arranged protein subunits can be resolved and (2) the haemagglutinin, a star-shaped structure about 350 A diameter made up of the spikes which project from the surface of the intact particle. Incomplete forms have been prepared by serial undiluted passage, and these show great pleomorphism, but the same outer coat as complete virus. Ether splitting of incomplete forms yields a haemagglutinin like that from complete virus, but only traces of G antigen. Virus N is more pleomorphic than KP virus, but the products of ether splitting are very similar.

Incomplete influenza virus prepared by multiple infection of allantoic cells has been examined in the electron microscope by negative staining. Such virus differed from standard (fully infective) virus in being grossly pleomorphic, and included some filamentous forms. It resembled standard virus in having a similar outer layer, and in showing no spontaneous disruption of the particles. Preparations of reactivated virus were made by multiplicity reactivation of inocula of ultra-violet irradiated virus, and these had a generally similar appearance, including some very long filamentous forms.

Measles virus has been disintegrated by treatment with ether and Tween 80. This destroys the infectivity, and physically disintegrates the particle, with the release of an inner component structurally like the nucleoprotein of Newcastle disease virus (NDV), and another structure similar to the haemagglutinin (HA) of NDV. The preparation after ether-tween treatment has an enhanced HA activity. The two components are separable in a CsCl density gradient. The inner component is probably a nucleoprotein. The HA component could be adsorbed by monkey erythrocytes but not eluted from them. The action on it of sodium metaperiodate suggests that a carbohydrate may be involved. The ether-tween preparation could be used as an antigen in the CF-reaction with antisera to rinderpest and distemper. It could also be used in the HA-inhibition test as a sensitive indicator with antisera to rinderpest and distemper, as well as to measles, giving higher titres in the HA-inhibition test than when the untreated virus was used. Injection of the ether-tween preparation stimulated the production of neutralizing, HA-inhibiting and complement-fixing antibodies in the rabbit.