Tumor suppressor interferonregulatory factor 1 counteracts the germinal center reaction driven by a cancerassociated gammaherpesvirus

Wadzanai P. Mboko, Horatiu Olteanu, Avijit Ray, Gang Xin, Eric J. Darrah, Suresh N. Kumar, Joseph M. Kulinski, Weiguo Cui, Bonnie N. Dittel, Stephen B. Gauld, Vera L. Tarakanova

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Gammaherpesviruses are ubiquitous pathogens that are associated with the development of B cell lymphomas. Gammaherpesviruses employ multiple mechanisms to transiently stimulate a broad, polyclonal germinal center reaction, an inherently mutagenic stage of B cell differentiation that is thought to be the primary target of malignant transformation in virus-driven lymphomagenesis. We found that this gammaherpesvirus-driven germinal center expansion was exaggerated and lost its transient nature in the absence of interferon-regulatory factor 1 (IRF-1), a transcription factor with antiviral and tumor suppressor functions. Uncontrolled and persistent expansion of germinal center B cells led to pathological changes in the spleens of chronically infected IRF-1-deficient animals. Additionally, we found decreased IRF-1 expression in cases of human posttransplant lymphoproliferative disorder, a malignant condition associated with gammaherpesvirus infection. The results of our study define an unappreciated role for IRF-1 in B cell biology and provide insight into the potential mechanism of gammaherpesvirus-driven lymphomagenesis.

Original languageEnglish (US)
Pages (from-to)2818-2829
Number of pages12
JournalJournal of virology
Volume90
Issue number6
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Tumor suppressor interferonregulatory factor 1 counteracts the germinal center reaction driven by a cancerassociated gammaherpesvirus'. Together they form a unique fingerprint.

Cite this