Tumorigenic poxviruses up-regulate intracellular superoxide to inhibit apoptosis and promote cell proliferation

Melissa LT Teoh-Fitzgerald, Patricia V. Turner, David H. Evans

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Tumorigenic leporipoxviruses encode catalytically inactive homologs of cellular Cu-Zn superoxide dismutase (SOD1). The function of the orthologous myxoma virus M131R and Shope fibroma virus S131R gene products is uncertain, but they inhibit SOD1 activity by a process linked to binding its copper chaperone. Using a superoxide-sensitive dye (hydroethidine), we observed that virus infection increased intracellular superoxide levels in an M/S131R-dependent manner. To see whether this effect promotes infection, we deleted the Shope fibroma virus S131R gene and compared the clinical manifestations of wild-type and mutant virus infections in rabbits. S131RA virus produced significantly smaller fibroxanthosarcoma-like growths in vivo and, at a point where these growths were already receding, wild-type infections still showed extensive leukocyte infiltration, necrosis, and fibromatous cell proliferation. Coincidentally, whereas Jurkat cells are protected from mitochondria- and Fas-mediated apoptosis by wild-type myxoma virus in vitro, M131RΔ virus could not block Fas-initiated apoptosis as judged by DNA laddering, terminal deoxynucleotidyltransferase-mediated dUTP-fluorescein nick end labeling, and caspase 3 cleavage assays. These data suggest that tumorigenic poxviruses can modulate intracellular redox status to their advantage to stimulate infected cell growth and inhibit programmed cell death.

Original languageEnglish (US)
Pages (from-to)5799-5811
Number of pages13
JournalJournal of virology
Volume79
Issue number9
DOIs
StatePublished - May 1 2005

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Poxviridae
Rabbit Fibroma Virus
Myxoma virus
Superoxides
superoxide anion
Rabbit fibroma virus
cell proliferation
Up-Regulation
apoptosis
Cell Proliferation
Virus Diseases
Apoptosis
viruses
Leporipoxvirus
Growth
infection
Viruses
Jurkat Cells
DNA Nucleotidylexotransferase
Infection

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Tumorigenic poxviruses up-regulate intracellular superoxide to inhibit apoptosis and promote cell proliferation. / Teoh-Fitzgerald, Melissa LT; Turner, Patricia V.; Evans, David H.

In: Journal of virology, Vol. 79, No. 9, 01.05.2005, p. 5799-5811.

Research output: Contribution to journalArticle

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