Neuronal apoptosis pathways in Sindbis virus encephalitis.

Sindbis virus infects neurons of the brain and spinal cord leading to neuronal apoptosis and encephalitis in mice. During postnatal development, neurons of mice remain susceptible to infection but become refractory to SV-induced programmed cell death. Failure to undergo programmed cell death results in a persistent infection. However, some neurovirulent strains of Sindbis virus overcome the age-dependent protective function in neurons, leading to enhanced apoptotic cell death in the central nervous system and higher mortality rates. Sindbis virus infections can also cause hind-limb paralysis due to the death of infected spinal cord motor neurons. However, spinal cord neuron death in older mice appears to occur by mechanisms that differ from classical apoptosis observed in newborn mice based on the morphology of dying neurons at these two sites. Sindbis virus infections of mosquitoes and some mosquito cell lines, on the other hand, do not induce cell death but persistent infections, a phenomenon also observed occasionally in cultured mammalian cells as well as in brains of infected mice surviving lethal infections. Thus, both viral and cellular factors contribute to the varied outcomes of infection. The molecular mechanisms that govern the susceptibility or resistance of particular cell types to SV-induced cell death are not well understood. Furthermore, the cellular execution machinery that produces the characteristic morphological distinctions between brain and spinal cord (i.e. apoptotic versus non-apoptotic) remain to be discovered.