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Journal of Virology, December 2005, p. 14562-14569, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14562-14569.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Protection from Interferon-Induced Apoptosis by Epstein-Barr Virus Small RNAs Is Not Mediated by Inhibition of PKR

Ingrid K. Ruf,1* Kristen A. Lackey,2 Swati Warudkar,2 and Jeffery T. Sample1,3*

Department of Biochemistry, MS340, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105,1 Department of Molecular Biology and Biochemistry, 3236 McGaugh Hall, University of California, Irvine, California 92697,2 Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee 381633

Received 7 July 2005/ Accepted 7 September 2005

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 {alpha} subunit of eukaryotic initiation factor 2 (eIF-2{alpha}), 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.

* Corresponding author. Present address for I. K. Ruf: Department of Molecular Biology and Biochemistry, 3236 McGaugh Hall, University of California, Irvine, CA 92697. Phone: (949) 824-4485. Fax: (949) 824-8551. E-mail: iruf{at}uci.edu. Mailing address for J. T. Sample: Department of Biochemistry, MS340, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105. Phone: (901) 495-3467. Fax: (901) 525-8025. E-mail: jeff.sample{at}stjude.org.

Journal of Virology, December 2005, p. 14562-14569, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14562-14569.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fok, V., Friend, K., Steitz, J. A. (2006). Epstein-Barr virus noncoding RNAs are confined to the nucleus, whereas their partner, the human La protein, undergoes nucleocytoplasmic shuttling. JCB 173: 319-325 [Abstract] [Full Text]  
  • Fok, V., Mitton-Fry, R. M., Grech, A., Steitz, J. A. (2006). Multiple domains of EBER 1, an Epstein-Barr virus noncoding RNA, recruit human ribosomal protein L22. RNA 12: 872-882 [Abstract] [Full Text]  
  • CONRAD, N.K., FOK, V., CAZALLA, D., BORAH, S., STEITZ, J.A. (2006). The Challenge of Viral snRNPs. Cold Spring Harb Symp Quant Biol 71: 377-384 [Abstract]  


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