Submitted to: Current Topics in Microbiology and Immunology
Publication Type: Review article
Publication Acceptance Date: 11/1/2001
Publication Date: N/A
Citation: Interpretive Summary:
Technical Abstract: The clearance of virus from many tissues involves cytotoxic immune responses that can often cause substantial damage with limited functional impairment due to regeneration and repair mechanisms. This is not the case for the CNS where destruction of neurons has severe consequences whether it is caused by the virus or the anti-viral immune response. Where a CNS infection results in cytolysis, early control of virus replication and virus spread is critical for neuronal and, ultimately, host survival. However, an immune response that is protective elsewhere could readily cause severe disease in the process of clearing an infection from the CNS. If virus can be cleared from the CNS without killing infected neurons it may be expected that non-cytolytic mechanisms involving antibody, cytokines and chemokines play a central role. Nevertheless, studies of different neurotropic virus infections indicate that both humoral and cellular immune eresponses are necessary for viral clearance from the CNS. The balance of the different antiviral immune effector mechanisms involved in clearance of virus from the CNS in part dictates the extent of the immunopathology that is often a major consequence of the antiviral response. The extent of infection when a virus-clearing response reaches the CNS is also extremely important in this regard. If immunity develops after significant virus replication and spread through the CNS a cytopathic immune effector mechanism would be expected to cause severe immunopathological consequences. In the absence of immunopathology, the outcome of the infection would depend upon the inherent pathogenicity of the virus. In this chapter we will discuss how different immune responses contribute to the clearance of virus from the CNS, using two highly neurotropic viruses.