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Hepatitis Mutants of Mouse Hepatitis Virus Strain A59

  • S. T. Hingley
  • J. L. Gombold
  • E. Lavi
  • S. R. Weiss
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 380)

Abstract

MHV-A59 causes acute meningoencephalitis and hepatitis in susceptible mice, and a persistent productive, but nonlytic, infection of cultured glial cells. We have shown previously that viruses isolated from persistently infected glial cell cultures have a fusion-defective phenotype and were impaired in their abilities to cause hepatitis compared to wild-type MHV-A59. Two mutants chosen for detailed study, B11 and C12, display two distinct hepatitis phenotypes. The ability of B11 to replicate in the liver was dependent on infectious dose and route of inoculation, while C12 consistently displayed decreased liver titers regardless of dose and route of inoculation. Sequence analysis of wild-type, mutant and revertant S proteins indicates that 1) a mutation in the N terminal subunit of S, resulting in a glutamine to leucine amino acid substitution (Q159L), may affect ability to cause hepatitis and 2) a cleavage site mutation (H716D) which determines fusogenicity is not responsible for the altered hepatitis phenotype. Sequence analysis indicated that hepatitis-producing revertants did not revert at mutation Q159L, although it is possible that a mutation in the heptad repeat domain of S2 may compensate for the mutation in S1. Since Bll, C12 and a nonattenuated fusion mutant (B12) have identical S protein sequences, there must be additional mutations outside of S which influence both virulence and ability to replicate in the liver.

Keywords

Mouse Fibroblast Cell Susceptible Mouse Mouse Hepatitis Virus Fusion Mutant Murine Coronavirus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • S. T. Hingley
    • 1
  • J. L. Gombold
    • 2
  • E. Lavi
    • 3
  • S. R. Weiss
    • 4
  1. 1.Department of Microbiology and ImmunologyPhiladelphia College of Osteopathic MedicinePhiladelphiaUSA
  2. 2.Department of Microbiology and ImmunologyLouisiana State University Medical CenterShreveportUSA
  3. 3.Department of PathologyUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of MicrobiologyUniversity of PennsylvaniaPhiladelphiaUSA

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