Apoptosis in alphavirus encephalitis

Sindbis virus causes acute encephalitis in mice and serves as a useful mode l for encephalitic alphaviruses that infect humans. The outcome of infectio n is determined by whether infected neurons are resistant to virus-induced programmed cell death or activate their apoptotic pathway. The host immune response may also cause death of infected neurons. Determinants of neuronal apoptosis include the maturity of the neuron, the virulence of the infecti ng virus and the cellular immune response to infection, in many situations viral and cellular factors that decrease virus replication also decrease ap optosis. Antiviral antibody can downregulate virus replication in surviving neurons without affecting cell viability Other innate and induced host imm une responses can alter the outcome of infection without a change in virus production. Failure to induce apoptosis in infected neurons leads to long-t erm persistence of small amounts of viral RNA in the nervous system of infe cted mice despite the clearance of infectious virus. The molecular mechanis ms that govern these pathogenesis factors are beginning to be elucidated. ( C) 1998 Academic Press.