The art of survival during viral persistence.
Central nervous system infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in chronic demyelination characterized by viral persistence in the absence of infectious virus. CD8(+) T cells inhibit acute viral replication via cell type-specific effector mechanisms. Perforin-mediated cytolysis controls virus in microglia/macrophages and astrocytes, whereas interferon (IFN)-gamma regulates viral replication in oligodendroglia. JHMV infection of antibody-deficient mice confirmed a primary role of cellular immunity and a redundant role for humoral immunity during acute infection. However, infectious virus reactivates in antibody-deficient mice following viral clearance. This observation suggests that virus-specific T cells in the central nervous system are unable to control viral persistence. Reactivation in antibody-deficient mice is not associated with increased T-cell infiltration, but is prevented via transfer of neutralizing antibody. A vital role for humoral immunity during persistence is supported by the accumulation and retention of virus-specific antibody secreting cells following clearance of infectious virus. Thus, cell-mediated immune responses control acute infection, whereas humoral immunity maintains viral persistence. Therefore, although the central nervous system provides an environment for prolonged retention of both T cells and plasma cells, plasma cells are critical in maintaining persistent virus at undetectable levels. The low turnover of virus, T cells, and B cells constitute a unifying feature of persistent infection, illustrating the dichotomy between distinct immune effectors in regulating acute and persistent central nervous system infection.
Stohlman
Stephen A
SA
Department of Neurology, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. stohlman@usc.edu
Ramakrishna
Chandran
C
Tschen
Shuen-Ing
SI
Hinton
David R
DR
Bergmann
Cornelia C
CC
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018352:Coronavirus Infections / Q000276:immunology* / Q000821:virology*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000821:virology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D006517:Murine hepatitis virus / Q000254:growth & development* / Q000302:isolation & purification; D010950:Plasma Cells / Q000276:immunology / Q000821:virology; D014779:Virus Replication
D000914:Antibodies, Viral; D000956:Antigens, Viral