The effects of alphavirus infection on neurons.

Sindbis virus is an alphavirus that causes encephalitis in mice. The primary target cells for central nervous system infection are neurons. The outcome of neuronal infection is dependent on the age of the mouse at the time of infection (maturity of the neuron) and the strain of virus used for infection (virulence of the virus). Sindbis virus causes neuronal death by inducing apoptosis. As neurons mature, they become resistant to virus-induced apoptosis, resulting in a persistent infection. Host production of antibody to a viral surface glycoprotein acts to downregulate virus replication in the infected neurons by a noncytolytic mechanism and clears infectious virus from the central nervous system. Specific genetic changes in the virus result in more virulent strains that cause severe disease and sometimes death in mature animals. These same genetic alterations also confer the ability to overcome the resistance of neurons to induction of cell death. Therefore, mature neurons infected with virulent viruses do not recover from infection even in the presence of an adequate immune response.