Clearance of virus infection from the CNS

Viruses that cause encephalomyelitis infect neurons and recovery from infection requires noncytolytic clearance of virus from the nervous system to avoid damaging these irreplaceable cells. Several murine model systems of virus infection have been used to identify clearance mechanisms. Quantitative analysis of Sindbis virus clearance over 6 months shows three phases: day 5–7, clearance of infectious virus, but continued presence of viral RNA; day 8–60, decreasing levels of viral RNA; day 60–180, maintenance of viral RNA at low levels. Antiviral antibody and interferon-γ have major roles in clearance with a likely role for IgM as well as IgG antibody. Long-term residence of virus-specific immune cells in the nervous system is necessary to prevent virus reactivation.

► Recovery from viral encephalomyelitis requires a noncytolytic process for clearance of virus from neurons. ► Noncytolytic clearance of virus from neurons is dependent on antiviral antibody and IFN-γ produced by cells infiltrating the CNS. ► After clearance of infectious virus, viral RNA is slowly cleared, but remains at low levels. ► Long-term presence of residual viral RNA requires local antibody-secreting cells to prevent virus reactivation.