Dominant inhibitory Ras delays Sindbis virus-induced apoptosis in neuronal cells

Andrew K. Joe, Giovanna Ferrari, Hui Hui Jiang, Xiao Huan Liang, Beth Levine

Research output: Contribution to journalArticle

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Abstract

Mature neurons are more resistant than dividing cells or differentiating neurons to Sindbis virus-induced apoptotic death. Therefore, we hypothesized that mitogenic signal transduction pathways may influence susceptibility to Sindbis virus-induced apoptosis. Since Ras, a 21-kDa GTP-binding protein, plays an important rule in cellular proliferation and neuronal differentiation, we investigated the effect of an inducible dominant inhibitory Ras on Sindbis virus-induced death of a rat pheochromocytoma cell line, PC12 cells. Dexamethasone induction of dominant inhibitory Ras (Ha Ras(Asn17)) expression in transfected PC12 cell lines (MMTV-M17-21 and GSrasDN6 cells) resulted in a marked delay in Sindbis virus-induced apoptosis, compared with infected, uninduced cells. The delay in death after Sindbis virus infection in induced versus uninduced PC12 cells was not associated with differences in viral titers or vital infectivity. No delay in Sindbis virus-induced apoptosis was observed in Ha Ras(Asn17)-transfected PC12 cells if dexamethasone induction was initiated less than 12 h before Sindbis virus infection or in wild-type PC12 cells infected with a chimeric Sindbis virus construct that expresses Ha Ras(Asn17). The delay in Sindbis virus-induced apoptosis in induced Ha Ras(Asn17)-transfected PC12 cells was associated with a decrease in cellular DNA synthesis as measured by 5'- bromo-2'-deoxyuridine incorporation. Thus, in PC12 cells, inducible dominant inhibitory Ras inhibits cellular proliferation and delays Sindbis virus- induced apoptosis. These findings suggest that a Ras-dependent signaling pathway is a determinant of neuronal susceptibility to Sindbis virus-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)7744-7751
Number of pages8
JournalJournal of Virology
Volume70
Issue number11
StatePublished - Nov 1996

Fingerprint

Sindbis virus
Sindbis Virus
PC12 Cells
apoptosis
neurons
Apoptosis
cells
Virus Diseases
dexamethasone
death
Dexamethasone
cell proliferation
cell lines
Cell Proliferation
Neurons
Bromodeoxyuridine
viral load
G-proteins
GTP-Binding Proteins
infection

ASJC Scopus subject areas

  • Immunology

Cite this

Joe, A. K., Ferrari, G., Jiang, H. H., Liang, X. H., & Levine, B. (1996). Dominant inhibitory Ras delays Sindbis virus-induced apoptosis in neuronal cells. Journal of Virology, 70(11), 7744-7751.

Dominant inhibitory Ras delays Sindbis virus-induced apoptosis in neuronal cells. / Joe, Andrew K.; Ferrari, Giovanna; Jiang, Hui Hui; Liang, Xiao Huan; Levine, Beth.

In: Journal of Virology, Vol. 70, No. 11, 11.1996, p. 7744-7751.

Research output: Contribution to journalArticle

Joe, AK, Ferrari, G, Jiang, HH, Liang, XH & Levine, B 1996, 'Dominant inhibitory Ras delays Sindbis virus-induced apoptosis in neuronal cells', Journal of Virology, vol. 70, no. 11, pp. 7744-7751.
Joe, Andrew K. ; Ferrari, Giovanna ; Jiang, Hui Hui ; Liang, Xiao Huan ; Levine, Beth. / Dominant inhibitory Ras delays Sindbis virus-induced apoptosis in neuronal cells. In: Journal of Virology. 1996 ; Vol. 70, No. 11. pp. 7744-7751.
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