Hemagglutinin-esterase-specific monoclonal antibodies alter the neuropathogenicity of mouse hepatitis virus.
Some of mouse hepatitis virus strains contain an optional envelope glycoprotein, hemagglutinin-esterase (HE) protein. To understand the functional significance of this protein, monoclonal antibodies (MAbs) specific for this protein were generated and used for passive immunization of mice. None of these MAbs showed any virus-neutralizing activity in vitro; however, mice passively immunized with the purified MAbs were protected from lethal infection by the JHM strain of mouse hepatitis virus. Passive immunization altered the pathogenicity such that the virus caused subacute and chronic demyelination instead of acute lethal encephalitis. Virus titers in the brains of the immunized mice were significantly lower than those for the nonimmunized control mice, suggesting that the virus replication or spread was inhibited. In addition, histopathological analysis indicated that the spread of virus in the brain and spinal cord was significantly inhibited in the immunized mice. Furthermore, the mononuclear cell infiltration in the immunized mice appeared earlier than in the nonimmunized mice, suggesting that the exogenous antibody might have activated host immune responses, and thus facilitated clearance of the virus or virus-infected cells. The same protective effects were observed for both JHM(2) and JHM(3) viruses, which expressed different amounts of the HE protein. In contrast, mice infected with At11f, a variant of JHM which does not express the HE protein, were not protected by these MAbs, suggesting that protection was mediated by the specific interaction between the MAb and the HE protein. Thus, the mechanism of protection by the exogenous HE-specific MAbs may represent the early activation of innate immune mechanisms in response to the interaction between the MAbs and the HE protein.
Yokomori
K
K
Howard Hughes Medical Institute, University of Southern California, School of Medicine, Los Angeles 90033-1054.
Baker
S C
SC
Stohlman
S A
SA
Lai
M M
MM
D000818:Animals; D000911:Antibodies, Monoclonal; D001254:Astrocytoma; D001921:Brain / Q000473:pathology; D002460:Cell Line; D002490:Central Nervous System / Q000473:pathology*; D003711:Demyelinating Diseases; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006518:Hepatitis Viruses / Q000201:enzymology* / Q000472:pathogenicity; D006524:Hepatitis, Viral, Animal / Q000473:pathology*; D007116:Immunization, Passive; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D013116:Spinal Cord / Q000473:pathology; D016019:Survival Analysis; D014760:Viral Fusion Proteins; D014764:Viral Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006389:Hemagglutinins, Viral; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C060814:hemagglutinin esterase