title: The art of survival during viral persistence.
abstract: 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.
authors.affiliation: Department of Neurology, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. stohlman@usc.edu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stohlman
authors.forename: Chandran
authors.initials: C
authors.lastname: Ramakrishna
authors.forename: Shuen-Ing
authors.initials: SI
authors.lastname: Tschen
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
authors.forename: Cornelia C
authors.initials: CC
authors.lastname: Bergmann
mesh_terms: 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
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral