Date of Award

1988

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Abstract

Serologically identical variants of encephalomyocarditis (EMC) virus produce different disease syndromes in mice. For instance, in ICR Swiss male mice, the B variant (EMC-B) produces no overt illness, EMC-MM produces death accompanied by eevere neurological signs, and EMC-0 destroys beta cells, thus producing a disease syndrome that resembles insulin-dependent diabetes mellitus. These apparently identical viruses provide excellent models to investigate the molecular basis of disease. Recently, we isolated a lethal variant (EMC-K) from the EMC-B virus stock and compared its characteristics to three other EMC virus variants, EMC-B, D, and MM. The present study was done to determine (i) the pathology produced in mice by each of the variants, (ii) the role of possible diff~rences in capsid proteins in mediating pathogenesis, and (iii) the ability of EMC-B to infect neuronal tissue.

The data show that EMC-K is a picornavirus belonging to the EMC group of viruses. EMC-K was found to induce IFN in vivo but not in vitro, and is sensitive the anti viral iii action of both exogenous administered or endogenously (Poly I:C) induced IFN. The tissue tropism of each of the v irus variants differed . For example, EMC-D replicates primarily in the pancreas and spleen, EMC-Bin the pancreas, EMC-Kin the medulla/brain stem, and EMC-MM in the cerebrum. The pathological lesions produced by each variant correlate well with virus titers. It was determined that VPl, the immunodominant coat protein, is more basic in EMC-K compared to EMC-B, indicating that the ability of these viruses to produce a specific disease syndrome may be due to subtle differences in their capsid proteins that are preferentially recognized by different cell types. The B variant was capable of infecting cells in the CNS when inoculated intracranially. Since EMC-Bis a good inducer of IFN, and detectable levels of this substance are found in the serum following ip inoculation, we postulate that IFN might be one of the factors which limits the replication of this virus in the CNS when the virus is administered via the ip route.

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