Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody.
Monoclonal hybridoma antibodies directed against the polypeptides of murine hepatitis virus-4 (JHM strain) were tested for their ability to alter the course of a normally lethal intracerebral virus challenge. Three monoclonal antibodies directed against two distinct epitopes on the E2 glycoprotein of MHV-4 protected mice against lethal virus challenge and converted the infection from fatal encephalomyelitis to demyelination. A single neutralizing antibody directed against a third epitope on E2 as well as seven nonneutralizing antibodies to E2, E1, and N polypeptides did not protect against challenge. In mice which received protective antibody, MHV-4 infection was not blocked, however, virus grew to lower titers in liver and brain, and virus replication in the CNS was more restricted than in unprotected mice. Decreased involvement of neurons in the brains of protected mice was observed, and no evidence of neuronal infection in the spinal cords was found. In contrast, oligodendrocytes were infected in the presence of protective antibody, and evidence of demylination associated with mononuclear cell infiltration was found. These studies demonstrate that antibody to a single epitope on a viral glycoprotein can substantially alter the course and phenotype of disease.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D004660:Encephalitis / Q000209:etiology*; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006524:Hepatitis, Viral, Animal / Q000150:complications; D007116:Immunization, Passive; D051379:Mice; D006517:Murine hepatitis virus / Q000276:immunology*; D009474:Neurons / Q000382:microbiology; D009836:Oligodendroglia / Q000382:microbiology; D013997:Time Factors; D014764:Viral Proteins / Q000276:immunology; D015678:Viral Structural Proteins
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006023:Glycoproteins; D014764:Viral Proteins; D015678:Viral Structural Proteins