Hepatitis mutants of mouse hepatitis virus strain A59.
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 B11, 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.
Hingley
S T
ST
Department of Microbiology and Immunology, Philadelphia College of Osteopathic Medicine, Pennsylvania, USA.
Gombold
J L
JL
Lavi
E
E
Weiss
S R
SR
D000818:Animals; D001921:Brain / Q000821:virology; D018352:Coronavirus Infections / Q000821:virology*; D005814:Genes, Viral; D006524:Hepatitis, Viral, Animal / Q000821:virology*; D008099:Liver / Q000821:virology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D009154:Mutation; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics*; D014779:Virus Replication
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus