A REVIEW OF ALPHAVIRUS REPLICATION IN NEURONS

Alphaviruses are important causes of mosquito-borne viral encephalitis . The prototype alphavirus, Sindbis virus, causes encephalomyelitis in mice. The primary target cell for nervous system infection is the neu ron. Thus, Sindbis virus infection of mice provides a model system for studying virus-neuron interactions. The outcome of infection is depen dent on the maturity of the targeted neurons and on the strain of Sind bis virus used for infection. Most Sindbis virus strains can induce pr ogrammed cell death or apoptosis in cultured lines of mammalian cells and in immature postmitotic neurons both in vitro and in vivo. As neur ons mature they become increasingly resistant to Sindbis virus-induced apoptosis presumably due to increased expression with differentiation of cellular antiapoptotic proteins. Therefore, in the absence of an e ffective immune response, these relatively avirulent strains of Sindbi s virus establish persistent nonfatal infection in mature neurons. Mor e virulent strains of Sindbis virus can overcome this intrinsic resist ance of mature neurons to apoptosis and cause neuronal death. Amino ac id changes in the virion glycoproteins are the main determinants of ne urovirulence and knowledge of the effects of specific changes allows t he investigator to design Sindbis viruses of specified neurovirulence for animals of different ages. (C) 1998 Elsevier Science Ltd. All righ ts reserved.