THE ROLE OF ANTIBODY IN RECOVERY FROM ALPHAVIRUS ENCEPHALITIS

Alphaviruses infect neurons in the brain and spinal cord and cause acu te encephalomyelitis in a variety of mammals. The outcome of infection is determined by whether the neurons survive infection and this, in t urn, is determined by the virulence of the virus and the age of the ho st at the time of infection. We have been studying Sindbis virus (SV) infection of mice as a model system for alphavirus-induced encephalomy elitis. investigation of intracerebral infection of weanling mice with two different strains of SV has allowed us to analyze the role of the immune response in protection from fatal disease (virulent NSV strain ) and in clearance of virus from the nervous system during non-fatal d isease (less virulent SV AR339 strain). Neutralizing and non-neutraliz ing antibodies to the El and E2 surface glycoproteins can protect mice from fatal NSV infection when given before or after infection, while T cells are not protective. The mechanism of antibody-mediated protect ion is not known, but it is likely that more than one mechanism is inv olved and that different mechanisms are involved in pre-infection and post-infection treatment protection. Clearance of infectious virus fro m the nervous system of mice during recovery from non-fatal disease is accomplished by antibodies to the E2 glycoprotein. The process does n ot involve damage to the infected neurons and is independent of comple ment and mononuclear cells. Bivalent antibody is required and binds to the surface of the infected cell. Initially release of virus by buddi ng from the cell surface is prevented and, subsequently, intracellular virus replication is inhibited possibly through antiviral mechanisms induced in co-operation with interferon. This non-lytic mechanism for control of virus infection results in the prolonged presence of viral RNA in tissue and the need for prolonged intrathecal synthesis of anti viral antibody by B cells within the central nervous system.