Cytomegalovirus contributes to glioblastoma in the context of tumor suppressor mutations

Richard L. Price, Jieun Song, Katherine Bingmer, Tae Hyong Kim, Ji Yeun Yi, Michal O. Nowicki, Xiaokui Mo, Todd Hollon, Eric Murnan, Christopher Alvarez-Breckenridge, Soledad Fernandez, Balveen Kaur, Andreana Rivera, Michael Oglesbee, Charles Cook, E. Antonio Chiocca, Chang Hyuk Kwon

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

To study the controversial role of cytomegalovirus (CMV) in glioblastoma, we assessed the effects of murine CMV (MCMV) perinatal infection in a GFAP-cre; Nf1loxP/+; Trp53-/+ genetic mouse model of glioma (Mut3 mice). Early on after infection, MCMV antigen was predominantly localized in CD45+ lymphocytes in the brain with active viral replication and local areas of inflammation, but, by 7 weeks, there was a generalized loss of MCMV in brain, confirmed by bioluminescent imaging. MCMV-infected Mut3 mice exhibited a shorter survival time from their gliomas than control Mut3 mice perinatally infected with mock or with a different neurotropic virus. Animal survival was also significantly shortened when orthotopic gliomas were implanted in mice perinatally infected with MCMV versus controls. MCMV infection increased phosphorylated STAT3 (p-STAT3) levels in neural stem cells (NSC) harvested from Mut3 mice subventricular zone, and, in vivo, there was increased p-STAT3 in NSCs in MCMV-infected compared with control mice. Of relevance, human CMV (HCMV) also increased p-STAT3 and proliferation of patient-derived glioblastoma neurospheres, whereas a STAT3 inhibitor reversed this effect in vitro and in vivo. These findings thus associate CMV infection to a STAT3-dependent modulatory role in glioma formation/progression in the context of tumor suppressor mutations in mice and possibly in humans.

Original languageEnglish (US)
Pages (from-to)3441-3450
Number of pages10
JournalCancer research
Volume73
Issue number11
DOIs
StatePublished - Jun 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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