Inhibition of virus-induced neuronal apoptosis by Bax

Jennifer Lewis, George A. Oyler, Kazuyoshi Ueno, Yih Ru Fannjiang, B. Nelson Chau, James Vornov, Stanley J. Korsmeyer, Shifa Zou, J Marie Hardwick

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)832-835
Number of pages4
JournalNature Medicine
Volume5
Issue number7
DOIs
StatePublished - Jul 1999

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Sindbis Virus
Viruses
Apoptosis
Neurons
Cell death
Cell Death
bcl-2-Associated X Protein
Spinal Ganglia
Virus Diseases
Inhibition (Psychology)
Parturition
Mortality
Infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lewis, J., Oyler, G. A., Ueno, K., Fannjiang, Y. R., Chau, B. N., Vornov, J., ... Hardwick, J. M. (1999). Inhibition of virus-induced neuronal apoptosis by Bax. Nature Medicine, 5(7), 832-835. https://doi.org/10.1038/10556

Inhibition of virus-induced neuronal apoptosis by Bax. / Lewis, Jennifer; Oyler, George A.; Ueno, Kazuyoshi; Fannjiang, Yih Ru; Chau, B. Nelson; Vornov, James; Korsmeyer, Stanley J.; Zou, Shifa; Hardwick, J Marie.

In: Nature Medicine, Vol. 5, No. 7, 07.1999, p. 832-835.

Research output: Contribution to journalArticle

Lewis, J, Oyler, GA, Ueno, K, Fannjiang, YR, Chau, BN, Vornov, J, Korsmeyer, SJ, Zou, S & Hardwick, JM 1999, 'Inhibition of virus-induced neuronal apoptosis by Bax', Nature Medicine, vol. 5, no. 7, pp. 832-835. https://doi.org/10.1038/10556
Lewis J, Oyler GA, Ueno K, Fannjiang YR, Chau BN, Vornov J et al. Inhibition of virus-induced neuronal apoptosis by Bax. Nature Medicine. 1999 Jul;5(7):832-835. https://doi.org/10.1038/10556
Lewis, Jennifer ; Oyler, George A. ; Ueno, Kazuyoshi ; Fannjiang, Yih Ru ; Chau, B. Nelson ; Vornov, James ; Korsmeyer, Stanley J. ; Zou, Shifa ; Hardwick, J Marie. / Inhibition of virus-induced neuronal apoptosis by Bax. In: Nature Medicine. 1999 ; Vol. 5, No. 7. pp. 832-835.
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