Protection from interferon-induced apoptosis by Epstein-Barr virus small RNAs is not mediated by inhibition of PKR

Ingrid K. Ruf, Kristen A. Lackey, Swati Warudkar, Jeffery T. Sample

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The Epstein-Barr virus (EBV) EBER transcripts are small, highly structured RNAs able to bind to and inhibit activation of the double-stranded RNA-dependent protein kinase PKR in cell-free systems, and within latently infected B-cell lines they inhibit alpha interferon-induced apoptosis that is believed to be mediated through PKR. Here, we address the consequences of EBER expression for PKR activation in vivo in response to alpha interferon. In agreement with published findings, either EBV infection or the EBERs alone protected Burkitt lymphoma cells from alpha-interferon-induced apoptosis. However, utilizing multiple phosphorylation state-specific antibodies to monitor PKR activation within cells in response to interferon, we demonstrate that the EBERs are unable to inhibit phosphorylation of either cytoplasmic or nuclear PKR. Concordantly, a direct substrate of PKR, the α subunit of eukaryotic initiation factor 2 (eIF-2α), was equally phosphorylated in EBV-positive and EBV-negative cells following interferon treatment. Therefore, EBER inhibition of alpha-interferon-induced apoptosis, and potentially other PKR-mediated events, is unlikely to be mediated through direct inhibition of PKR, as previously thought.

Original languageEnglish (US)
Pages (from-to)14562-14569
Number of pages8
JournalJournal of virology
Volume79
Issue number23
DOIs
StatePublished - Dec 1 2005

Fingerprint

Human herpesvirus 4
interferon-alpha
interferons
Human Herpesvirus 4
Interferon-alpha
Interferons
apoptosis
RNA
eIF-2 Kinase
Apoptosis
phosphorylation
Eukaryotic Initiation Factor-2
Phospho-Specific Antibodies
cell free system
Epstein-Barr Virus Infections
Burkitt Lymphoma
Double-Stranded RNA
Cell-Free System
double-stranded RNA
cells

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Ruf, Ingrid K. ; Lackey, Kristen A. ; Warudkar, Swati ; Sample, Jeffery T. / Protection from interferon-induced apoptosis by Epstein-Barr virus small RNAs is not mediated by inhibition of PKR. In: Journal of virology. 2005 ; Vol. 79, No. 23. pp. 14562-14569.
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Protection from interferon-induced apoptosis by Epstein-Barr virus small RNAs is not mediated by inhibition of PKR. / Ruf, Ingrid K.; Lackey, Kristen A.; Warudkar, Swati; Sample, Jeffery T.

In: Journal of virology, Vol. 79, No. 23, 01.12.2005, p. 14562-14569.

Research output: Contribution to journalArticle

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