Ole Sorensen

Date of Award


Degree Type


Degree Name

Doctor of Philosophy


The period of time between exposure to a possible causative agent and the first symptoms of multiple sclerosis (MS) can be measured in decades. This has made progress toward an understanding of the initial events in this disease difficult and so a number of animal models which mimic various aspects of the disease are being studied widely. JHM virus (JHMV) and MHV-3 virus infections of mice are among these models. Less attention has been paid to the interactions of these viruses with rats.;Rats and mice of various strains were challenged at various ages with MHV-3 or JHMV intracerebrally (IC) or interperitoneally (IP). The injections were monitored clinically, and by histology, electron microscopy, virology, and serology. The susceptibility of rats to JHMV was shown to be age-dependent and strain related. Wistar Furth rats suffered the highest mortality and were susceptible longer than other strains tested. Histological examination of rats dying during the first 2 weeks post inoculation (PI) indicated an encephalomyelitis while animals which survived longer tended to have only demyelinating lesions. Serum antibody levels did not appear to affect the outcome of infection although immunosuppression exacerbated an inapparent infection. F1 hybrids between sensitive and resistant rat strains indicated a dominance for the resistant trait.;F1 crosses between sensitive and resistant mouse strains were semiresistant to MHV-3 but displayed no change in susceptibility to JHMV. Natural killer cell deficient Beige mice were not unusually sensitive to JHMV while T-cell deficient Nude mice were susceptible to the virus. Mice were quickly protected from lethal IC challenge with JHMV by an IP inoculation wth the same virus. This protection was noted prior to increases in serum antibody levels and could not be ascribed to circulating interferon.;Based on these studies it appears that the age at inoculation, the genetic make-up and the competence of the immune system are the prime controls of coronavirus infection in both rats and mice. In view of the demyelinating disease provoked in a large proportion of Wistar Furth rats inoculated at the appropriate age, JHMV infection of this strain appears to be a suitable model for the study of progressive demyelinating disease.



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