Inhibition of virus-induced neuronal apoptosis by Bax

The Bax protein is widely known as a pro-apoptotic Bcl-2 family member that when overexpressed can trigger apoptosis in multiple cell types and is imp ortant for the developmental cell death of neurons(1,2). However, Bax was f ound here to be a potent inhibitor of neuronal cell death in mice infected with Sindbis virus. Newborn mice, which are highly susceptible to a fatal i nfection with neurotropic Sindbis virus, were significantly protected from neuronal apoptosis and fatal disease when infected with a recombinant Sindb is virus encoding Bar. Deletion of the N terminus of Bar, which mimics clea ved Bar, converted Bar into a pro-apoptotic factor in vivo. As mice mature during the first week after birth, they acquire resistance to a fatal Sindb is virus infection(3,4). However, Bax-deficient mice remained very sensitiv e to fatal disease compared with their control littermates, indicating that endogenous Bar functions as a survival factor and contributes to age-depen dent resistance to Sindbis virus-induced mortality. The protective effects of Bar were reproduced in cultured hippocampal neurons but not in cultured dorsal root ganglia neurons. These findings indicate that cell-specific fac tors determine the anti-apoptotic versus pro-apoptotic function of Bar.