Inhibition of virus-induced neuronal apoptosis by Bax

J Lewis1, G A Oyler, K Ueno

  • 1Department of Pharmacology and Molecular Sciences, Johns Hopkins University Schools of Medicine and Public Health, Baltimore, Maryland 21205, USA.

Nature Medicine
|July 8, 1999
PubMed

Insights

Bax protein normally promotes cell death but surprisingly inhibits neuronal death in Sindbis virus infections. Endogenous Bax acts as a survival factor, crucial for age-dependent resistance to fatal viral encephalitis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Immunology

Background:

  • Bax protein is a well-established pro-apoptotic member of the Bcl-2 family.
  • Overexpression of Bax typically induces apoptosis across various cell types.
  • Bax plays a role in developmental neuronal cell death.

Purpose of the Study:

  • To investigate the role of Bax in neuronal cell death during Sindbis virus infection.
  • To determine if Bax exhibits anti-apoptotic or pro-apoptotic functions in vivo and in vitro.
  • To elucidate the mechanism behind Bax's function in viral encephalitis.

Main Methods:

  • Infection of newborn mice with Sindbis virus, including recombinant viruses encoding Bax.
  • Analysis of neuronal apoptosis and disease severity in infected mice.
  • Assessment of Bax-deficient mice for susceptibility to Sindbis virus.
  • Studies on cultured hippocampal and dorsal root ganglia neurons.

Main Results:

  • Bax expression protected newborn mice from Sindbis virus-induced neuronal apoptosis and mortality.
  • Deletion of Bax's N-terminus reversed its function, making it pro-apoptotic in vivo.
  • Bax-deficient mice showed increased sensitivity to fatal Sindbis virus infection.
  • Bax conferred protection in hippocampal neurons but not dorsal root ganglia neurons.

Conclusions:

  • Bax functions as a potent inhibitor of neuronal cell death in the context of Sindbis virus infection.
  • Endogenous Bax acts as a survival factor, contributing to age-dependent resistance to viral encephalitis.
  • The pro- or anti-apoptotic function of Bax is cell-type specific, influenced by cellular factors.

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