Control of central nervous system viral persistence by neutralizing antibody.
Replication of the neurotropic JHM strain of mouse hepatitis virus within the central nervous system is controlled by cellular immunity. However, following initial clearance, virus reactivates in the absence of humoral immunity. Viral recrudescence is prevented by the transfer of antiviral antibody (Ab). To characterize the specificity and biological functions of Ab critical for maintaining viral persistence, monoclonal Abs specific for the viral spike, matrix, and nucleocapsid proteins were transferred into infected B-cell-deficient mice following initial virus clearance. Neutralizing immunoglobulin G (IgG) but not IgA anti-spike Ab suppressed virus recrudescence, reduced viral antigen in most cell types except oligodendroglia, and was associated with reduced demyelination. Nonneutralizing monoclonal Abs specific for the spike, matrix, and nucleocapsid proteins did not prevent recrudescence, demonstrating that neutralization is critical for maintaining JHM mouse hepatitis virus persistence within the central nervous system. Ab-mediated protection was not associated with alterations in virus-specific T-cell function or inflammation. Furthermore, neutralizing Ab delayed but did not prevent virus recrudescence. These data indicate that following acute viral clearance cellular immunity is ineffective in controlling virus recrudescence and suggest that the continued presence of neutralizing Ab is the essential effector in maintaining viral persistence within the central nervous system.
Ramakrishna
Chandran
C
Department of Neurology, USC Keck School of Medicine, Los Angeles, California 90033, USA.
Bergmann
Cornelia C
CC
Atkinson
Roscoe
R
Stohlman
Stephen A
SA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D002490:Central Nervous System / Q000821:virology*; D020805:Central Nervous System Viral Diseases / Q000821:virology*; D018352:Coronavirus Infections / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000472:pathogenicity / Q000502:physiology*; D009500:Neutralization Tests; D009836:Oligodendroglia / Q000821:virology; D014764:Viral Proteins / Q000276:immunology; D017735:Virus Latency / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014764:Viral Proteins