Inhibition of virus-induced neuronal apoptosis by Bax

Nat Med. 1999 Jul;5(7):832-5. doi: 10.1038/10556.


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 important for the developmental cell death of neurons. However, Bax was found 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 infection with neurotropic Sindbis virus, were significantly protected from neuronal apoptosis and fatal disease when infected with a recombinant Sindbis virus encoding Bax. Deletion of the N terminus of Bax, which mimics cleaved Bax, converted Bax into a pro-apoptotic factor in vivo. As mice mature during the first week after birth, they acquire resistance to a fatal Sindbis virus infection. However, Bax-deficient mice remained very sensitive to fatal disease compared with their control littermates, indicating that endogenous Bax functions as a survival factor and contributes to age-dependent resistance to Sindbis virus-induced mortality. The protective effects of Bax were reproduced in cultured hippocampal neurons but not in cultured dorsal root ganglia neurons. These findings indicate that cell-specific factors determine the anti-apoptotic versus pro-apoptotic function of Bax.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alphavirus Infections / genetics
  • Alphavirus Infections / pathology*
  • Alphavirus Infections / physiopathology
  • Animals
  • Apoptosis / physiology*
  • Brain / pathology*
  • Brain / virology*
  • Cell Line
  • Cells, Cultured
  • Cricetinae
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / physiology
  • Ganglia, Spinal / virology
  • Genetic Vectors
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Hippocampus / virology
  • Humans
  • Mice
  • Mice, Knockout
  • Neurons / pathology*
  • Neurons / physiology
  • Neurons / virology*
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2*
  • Rats
  • Rats, Sprague-Dawley
  • Sindbis Virus / isolation & purification
  • Sindbis Virus / pathogenicity*
  • Transfection
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Bax protein, mouse
  • Bax protein, rat
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein