Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in Vivo by monoclonal antibody

Abstract

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.

Antigenic and Polypeptide Structure of Turkey Enteric Coronaviruses as Defined by Monoclonal Antibodies

“…With purified viral preparations, a non-specific background of N protein was occasionally observed when anti-E2 and anti-E3 MAbs were tested, both by Western immunoblotting and immunoprecipitation experiments. Non-specific binding to N protein was also obtained in studies with other coronaviruses (Talbot et al, 1984;Laude et al, 1986;. The N protein is the most abundant structural component of the coronavirus virion (Siddell et al, 1983).…”

“…These data suggest that the critical antigenic determinants are probably conformation-dependent, as reported with other coronaviruses. Talbot et al (1984) found that three neutralization epitopes in MHV-JHM are sensitive to SDS denaturation, whereas in the case of transmissible gastroenteritis virus (TGEV), all six critical determinants are sensitive to SDS denaturation and 2-mercaptoethanol (Jim6nez et al, 1986).…”

“…The peplomeric E2 glycoprotein is often cleaved post-translationally by host cell proteases into two 85K to 100K subunits (Sturman et al, 1985;Cavanagh et al, 1986b). The latter also is known to be responsible for virus attachment and cell membrane fusion (Collins et al, 1982), and elicits the production of virus-neutralizing antibodies (Fleming et al, 1983;Laude et al, 1986;Niesters et al, 1987; which may be protective (Buchmeier et al, 1984;Wege et al, 1984;Cavanagh et al, 1986a). An additional glycoprotein of 130K to 140K, a disulphide-linked dimer of 65K subunits, is associated with the haemagglutinin (E3) of viruses belonging to the subgroup of haemagglutinating mammalian coronaviruses (King et al, 1985 ;Hogue & Brian, 1986: Sugiyama et al, I986).…”

Role of immune responses in protection and pathogenesis during Semliki Forest virus encephalitis

“…However, it is not unique: this phenomenon has also been described for Sindbis virus where it appears that anti-E2 monoclonal antibodies can mediate clearance of virus from CNS cells, perhaps by restricting viral gene expression (Levine et al, 1991). In addition to alphaviruses, antibodies are important in clearing virus from the CNS or initiating restricted replication in CNS cells in a number of other infections including TMEV, reovirus, rabies virus, mouse hepatitis virus and measles virus infections (Fujinami et al, 1989;Kurtz et al, 1995;Tyler et al, 1989;Perry & Lodmell, 1991 ;Buchmeier et al, 1984;Liebert et al, 1990).…”

Antibody Is Required for Clearance of Infectious Murine Hepatitis Virus A59 from the Central Nervous System, But Not the Liver

“…Instead, the relatively slowly responding B cells have been studied primarily as protectors against re-establishment of a viral infection. In accord with this protective role, B cell-derived Abs protect mice from the lethal effects of high dose MHV infection when transferred near the time of infection (11)(12)(13). However, the contrast of viral clearance in CD8 ϩ T cell-deficient mice with the lack of viral clearance in T and B cell-deficient RAG knockouts suggests that the B cell could be an additional potent viral regulator during a primary infection.…”