Epstein-barr virus independent dysregulation of UBP43 expression alters interferon-stimulated gene expression in Burkitt lymphoma

Ingrid K. Ruf, Jennifer L. Houmani, Jeffery T. Sample

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Epstein-Barr virus (EBV) persists as a life-long latent infection within memory B cells, but how EBV may circumvent the innate immune response within this virus reservoir is unclear. Recent studies suggest that the latency-associated non-coding RNAs of EBV may actually induce type I (antiviral) interferon production, raising the question of how EBV counters the negative consequences this is likely to have on viral persistence. We addressed this by examining the type I interferon response in Burkitt lymphoma (BL) cell lines, the only in vitro model of the restricted program of EBV latency-gene expression in persistently infected B cells in vivo. Importantly, we observed no effect of EBV on interferon alpha-induced signaling or evidence of type I interferon production, suggesting that EBV in this latent state is silent to the cell's innate antiviral surveillance. We did uncover, however, a defect in the negative feedback control of interferon signaling in a subpopulation of BL lines as was revealed by prolonged interferon-stimulated gene transcription consistent with sustained tyrosine phosphorylation on STAT1 and STAT2. This was due to inadequate induction of expression of the ubiquitin-specific protease UBP43, which removes the ubiquitin-like ISG15 polypeptide conjugated to proteins (ISGylation) in response to type I interferons. Results here are consistent with previous findings in genetically engineered Ubp43-/- murine cells that UBP43 down-regulates interferon signaling, independent of its ISG15 isopeptidase activity, by precluding the protein kinase JAK1 from the interferon receptor. This natural deficiency in UBP43 expression may therefore provide a useful model to further probe the biological roles of UBP43 and ISGylation.

Original languageEnglish (US)
Article numbere6023
JournalPloS one
Volume4
Issue number6
DOIs
StatePublished - Jun 24 2009

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Human herpesvirus 4
Burkitt Lymphoma
interferons
lymphoma
Human Herpesvirus 4
Viruses
Gene expression
Interferons
Interferon Type I
Gene Expression
gene expression
Cells
ubiquitin
Antiviral Agents
B-Lymphocytes
B-lymphocytes
Ubiquitin-Specific Proteases
Interferon Receptors
Virus Latency
Untranslated RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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abstract = "Epstein-Barr virus (EBV) persists as a life-long latent infection within memory B cells, but how EBV may circumvent the innate immune response within this virus reservoir is unclear. Recent studies suggest that the latency-associated non-coding RNAs of EBV may actually induce type I (antiviral) interferon production, raising the question of how EBV counters the negative consequences this is likely to have on viral persistence. We addressed this by examining the type I interferon response in Burkitt lymphoma (BL) cell lines, the only in vitro model of the restricted program of EBV latency-gene expression in persistently infected B cells in vivo. Importantly, we observed no effect of EBV on interferon alpha-induced signaling or evidence of type I interferon production, suggesting that EBV in this latent state is silent to the cell's innate antiviral surveillance. We did uncover, however, a defect in the negative feedback control of interferon signaling in a subpopulation of BL lines as was revealed by prolonged interferon-stimulated gene transcription consistent with sustained tyrosine phosphorylation on STAT1 and STAT2. This was due to inadequate induction of expression of the ubiquitin-specific protease UBP43, which removes the ubiquitin-like ISG15 polypeptide conjugated to proteins (ISGylation) in response to type I interferons. Results here are consistent with previous findings in genetically engineered Ubp43-/- murine cells that UBP43 down-regulates interferon signaling, independent of its ISG15 isopeptidase activity, by precluding the protein kinase JAK1 from the interferon receptor. This natural deficiency in UBP43 expression may therefore provide a useful model to further probe the biological roles of UBP43 and ISGylation.",
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Epstein-barr virus independent dysregulation of UBP43 expression alters interferon-stimulated gene expression in Burkitt lymphoma. / Ruf, Ingrid K.; Houmani, Jennifer L.; Sample, Jeffery T.

In: PloS one, Vol. 4, No. 6, e6023, 24.06.2009.

Research output: Contribution to journalArticle

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