Viruses: the versatile parasites; the arthropod-borne group of animal viruses.
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Biomedical subjects
Publications and source records attributed to J CASALS.
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Through the use of acetone and ether extraction of brain tissue from newborn mice infected with certain arthropod-borne viruses, it has been possible to demonstrate hemagglutinins for chick erythrocytes associated with the following viruses: dengue Type 1, dengue Type 2, Eastern equine encephalitis, Ilhéus, Japanese B, Ntaya, St. Louis, Sindbis, Uganda S, Venezuelan equine encephalitis, West Nile (Egypt 101 strain), Western equine encephalitis, and yellow fever (viscerotropic and neurotropic strains). On the basis of the temperature and pH required for reaction, the viruses can be assembled in two groups: A-those that require 37 degrees C. and a pH of about 6.4, comprising Eastern, Venezuelan, and Western equine encephalitis and Sindbis viruses; and B-those that require either 4 degrees or 22 degrees C. and a pH of about 7.0, comprising dengue Types 1 and 2, Ilhéus, Japanese B, Ntaya, St. Louis, Uganda S, West Nile, and yellow fever viruses. A method of eliminating non-specific inhibitory substances present in sera was developed. The method consists essentially of filtration through Seitz pads. Extensive serological crossings were found among viruses of each group, while antisera of one group failed consistently to cross-react with antigens of the other. Antisera deriving from animals immunized with certain viruses for which no hemagglutinins could be developed by the present method, reacted with members of either one or the other group. Thus Semliki Forest virus would appear to belong to Group A, and Russian Far Eastern and louping ill viruses to Group B.
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Sera from 81 patients with a diagnosis of paralytic or non-paralytic poliomyelitis, and from 159 individuals of similar age groups giving no history of the disease, were tested with a high titered, complement-fixing poliomyelitis antigen of Type 2 (Lansing-like). The antigen consisted of brain tissue from newborn mice injected with the MEF1 strain of virus as previously adapted to these animals. The presence or absence of Type 2 neutralizing antibody in the sera under test was found not to affect the complement fixation. Positive reactions were obtained with 57 per cent of the sera deriving from non-paralytic patients and in 70 per cent from paralytics, when the specimens were tested at a dilution of 1:16. The complement-fixing antibody was often present in highest titer as early as 24 hours after the onset of poliomyelitis, and in almost all instances within 7 days. In about half of the patients a 4-fold or greater drop in titer occurred within 3 months, with little or no change in the others. The incidence of titers of 1:16 or higher with the control sera varied with the season of the year at which they were procured, 3 per cent of the winter samples proving positive and 13 per cent of the summer. The tests of sera from the group of patients from whom poliomyelitis virus was recovered, disclosed no significant differences between those having the paralytic and those having the non-paralytic disease. Type 1 (Brunhilde-like) strains of virus were recovered from many of the patients yielding positive tests, although they presented no evidence of previous or concurrent infection with Type 2 virus. This finding shows that Type 1 virus can give rise in patients to Type 2 complement-fixing antibody. The application of these data to the serologic diagnosis of poliomyelitis infection in man will of necessity be limited until information is obtained on the development, persistence, and significance of complement-fixation reactions with antigens deriving from Type 1 and Type 3 poliomyelitis strains.
CF tests with Type 2 poliomyelitis antigen (MEF1) were performed on the pre- and postinfection sera of 20 cynomolgus monkeys which developed paralytic, non-paralytic, or inapparent infection following oral administration of a Type 2 strain of virus (Y-SK). All the monkeys developed neutralizing antibody, and 17 developed CF antibody in an original serum dilution titer of 1:4 or greater. The 3 monkeys which did not develop this level of CF antibody were in a group of 7 which died within 8 days after onset of paralysis. The CF titers were as high at 2 to 6 days after onset of paralysis in the other 4 moribund or dead monkeys as in the surviving animals tested 4 weeks after the first dose of virus and the CF titers were of the same order of magnitude in the groups with paralytic, non-paralytic, or inapparent infection. The Type 2 poliomyelitis CF titers developed in monkeys as a result of infection with homotypic virus were not greater than those found in human beings infected with heterotypic Type 1 poliomyelitis strains.
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By means of rapid serial passages, including 3 successive "blind" passages, the MEF1 strain, a Lansing-type poliomyelitis virus, has been adapted to new-born mice. The virus can readily be propagated in newborn mice, in which fully adapted virus induces in almost all inoculated animals the experimental disease, resulting in a much greater infectivity for the central nervous system and a uniformly short and regular incubation period.
A complement-fixing antigen has been developed, using as source of material CNS tissue from newborn mice infected with the newborn mouse-adapted strain of the Lansing type, MEF1 virus. With this antigen, specific reactions have been obtained with sera from mice, cotton rats, and monkeys immunized with the Lansing-type virus, and from monkeys and chimpanzees convalescent from infection with this virus. Twenty-one of 35 human sera obtained from individuals convalescent from poliomyelitis were positive and 6 of 22 from apparently normal persons having Lansing-neutralizing antibody, while this held true for only 1 of 19 from those having no Lansing-neutralizing antibody. The fact that positive results were found in sera from patients having an infection with poliomyelitis virus of the Brunhilde type and at the same time no Lansing-neutralizing antibody brings up the possibility of the existence of a cross-reaction in complement fixation between the two types.
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