Correlated autoradiographic and biochemical study of DNA labeling in equine abortion virus hepatitis.
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Observations on the behavior of MHV (Pr) in the cerebral tissue of Princeton and Swiss weanling mice indicated a limited neurotropism. The virus migrated to the brain on intraperitoneal injection and was established there by cranial passage, though with difficulty in Swiss mice. Intracerebral multiplication was rarely followed by outward signs of nervous disorder. A slight pathologic reaction occurred in the brains of intracerebrally injected Princeton mice, but it was negligible compared with that of the ensuing hepatitis. In Swiss mice, injected intracerebrally with a mixture of MHV (Pr) and Eperythrozoon coccoides, a related virus with restricted pathogenicity and host range, possibly a mutant, was isolated from the liver and brain. MHV (C), an actively hepatotropic virus recovered from leukemic Balb C mice, was much more neurotropic than MHV (Pr). Intracerebral injection of Balb C and Swiss weanling mice was attended by marked leptomeningeal and encephalitic lesions. Paralysis of the extremities occurred in some of the animals. The virus was essentially inactive in Princeton mice. During the intracerebral passage of MHV (C) in Swiss mice a pleuropneumonia-like organism was isolated from the brain. In conjunction with the virus this organism produced a vigorous leukocytic reaction.
The mortality rate for 80 Swiss weanlings infected with mouse hepatitis was 2.5 per cent in comparison with 98 per cent for 140 Princeton weanlings. In Swiss weanlings discrete lesions, which generally failed to progress, were observed in the liver from the 3rd through the 10th day after intraperitoneal injection. The causal virus was demonstrable in peritoneal washings through the 21st day and less regularly in the liver through the 14th day. It was also detectable in both loci after subcutaneous injection. Infant Swiss mice were susceptible through the 10th day of life, intraperitoneal injection being commonly followed by death. The pathogenicity and titer of the virus were significantly increased by successive passage in Swiss weanlings. The virus was detected in the blood of Swiss weanlings on subcutaneous injection only after it had been modified by passage.
The hepatitis of Princeton weanlings was not prevented by the prior injection of terramycin nor was the virus inactivated by exposure to room temperature. Eperythrozoon coccoides was not demonstrable in blood films from Swiss and Princeton mice infected with the corresponding type of hepatitis virus. Combined infection with this virus and eperythrozoa, originally obtained by Dr. R. B. McGhee from mice in association with Plasmodium berghei, was attended by the appearance of numerous organisms in the blood. The development of eperythrozoa in dually infected Princeton mice had no effect on the outcome of the hepatitis. In Swiss mice, animals with high natural resistance to hepatitis virus, the pathogenicity of this agent was markedly enhanced by combined infection with eperythrozoa. Eperythrozoa were maintained throughout 18 successive passages in normal Princeton and Swiss weanlings with intact spleens. The combined infection of Princeton mice with eperythrozoa and the virus component of Gledhill, Dick, and Andrewes, which is nearly inactive when injected alone, resulted in acute hepatitis with fatal outcome.
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