THE MODIFYING EFFECTS OF BACTERIAL SUBSTANCES IN THE COURSE OF INFECTION WITH NEUROTROPIC VIRUS

Abstract

The investigation of Shope (1) concerning the etiology of the swine influenza may be the first experiment on the interaction between a virus and a bacterium. Shope discovered that the disease was caused by a symbiosis of the bacillus, H. influenzae suis, and a virus, i.e, the bacillus alone would not produce the disease; the virus alone produced an extremely mild, but spontaneously transmissible infection. Both agents were needed to reproduce the clinical syndrome. Horsfall and McCarty (2) reported a study on the effects of inoculating mice with both a virus and a bacterium in the course of investigations concerned with problems relative to the pathogenesis of primary atypical pneumonia. They considered that, when the first experiments were carried out, either of two possible results might develop; first, that streptococcus MG would have no discernible influence on the course of an infection induced by pneumonia virus of mice (PVM); or second, that it might, by contributing to the establishment of a complex infection, cause the results to be more severe than those of infections induced by PVM alone. However they found that, surprisingly, neither possibility evolved; instead, the inoculation of streptococcus MG in mice which previously had been inoculated with PVM resulted in a distinctly less severe infection. After investigating on this unexpected finding in detail, they obtained certain polysaccharide preparations derived from various bacterial species, as well as similar materials from various origins other than bacteria, as agents of the modifying effect in the course of infection with PVM. Thereafter, they (3) (4) (5) (6) (7) studied on the inhibitory effect of polysaccharide derived from the bacterial origins on mumps virus multiplication. Volkert, Pierce, Horsf all, and Dubos (8) showed that following infection with small amounts of either PVM or influenza A virus (PR 8) intranasally, tuberculous lesions in the lungs of mice developed more rapidly and became more extensive than in control animals infected only with tubercle bacilli. Recently, Buddingh (9) reported that combinated viral and bacterial infection established by intra-amniotic inoculation with influenza C virus on the 14th followed by H. influenzae, type b, brought about a significant increase in the incidence and severity of disease manifestations in the embryos, and that there seemed to be relatively little or no effect on influenza C virus by the accompanying proliferation of H. influenzae, and finally that the exact nature of the virus-induced influences which enhanced the pathogenicity of the bacteria and favored the establishment of the infectious process under these circumstances remained to be determined. Stone (10) (11) expressed that, receiving suggestions from Hirst's discovery of the phenomenon of hemagglutination by influenza virus (12) and of being a somewhat similar reaction between this virus and cells of the excised ferret lung (13), infection by influenza viruses of embryonated eggs after allantoic inoculation, and of mouse lungs after intranasal instillation, could be prevented by pretreatment of the exposed cells with the receptor-destroying enzyme (RDE) of V, cholerae (14). Cairns (15) demonstrated also that death of mice from infection by a neurotropic variant of influenza virus could be similarly prevented following an intracerebral injection of RUE. The results obtained by seniors mentioned above, however, are that of relationships between pneumotropic viruses and bacteria, and at present there is very few studies on the interaction between neurotropic viruses and bacteria. Goto and others (16) (17) and Hayashi and others (18) reported some detail experiments on the inhibitory effects of bacterial polysaccharide in the course of infection with Japanese B encephalitis virus. Nakagawa and Yoshida (19) described an experiment on the neurotropic virus-bacteria relationship in which the infection with the GDVII strain of mouse enceph