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Molecular and Cellular Biology, November 1999, p. 7305-7313, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Sensitivity of an Epstein-Barr Virus-Positive Tumor Line, Daudi, to Alpha Interferon Correlates with Expression of a GC-Rich Viral Transcript

Yanning Gao,dagger Shao-an Xue,Dagger and Beverly E. Griffin*

Department of Infectious Diseases (Virology), Imperial College School of Medicine, London W12 0NN, United Kingdom

Received 25 January 1999/Returned for modification 8 March 1999/Accepted 11 August 1999

The exquisite sensitivity of the Burkitt's lymphoma (BL)-derived cell line Daudi to type I interferons has not previously been explained. Here we show that expression of an Epstein-Barr virus (EBV) transcript, designated D-HIT (Y. Gao et al., J. Virol. 71:84-94, 1997), correlates with the sensitivity of different Daudi cell isolates (or that of other EBV-carrying cells, where known) to alpha interferon (IFN-alpha ). D-HIT, transcribed from a GC-rich repetitive region (IR4) of the viral genome, is highly structured, responding to RNase digestion in a manner akin to double-stranded RNA. Comparing EBV-carrying BL cell lines with differing responses to IFN-alpha , we found the protein levels of the dsRNA-activated kinase, PKR, to be similar, whereas the levels of the autophosphorylated active form of PKR varied in a manner that correlated with endogenous levels of D-HIT expression. In a classical in vitro kinase assay, addition of either poly(I)-poly(C) or an in vitro-transcribed D-HIT homolog stimulated the autophosphorylation activity of PKR from IFN-alpha -treated cells in both EBV-positive and EBV-negative B lymphocytes. By transfection experiments, these RNAs were shown to reduce cell proliferation and to sensitize otherwise relatively insensitive Raji cells to IFN-alpha . The data lead to a model wherein the D-HIT viral RNA also serves as a possible transcriptional activator of IFN-alpha or cellular genes regulated by this cytokine.

* Corresponding author. Present address: Viral Oncology Unit, Division of Medicine, Imperial College of Medicine, St. Mary's site, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 171 594 3670. Fax: 44 171 402 1037. E-mail: bgriffin{at}ic.ac.uk.

dagger Present address: Cancer Research Institute, CAMS, Beijing 100021, People's Republic of China.

Dagger Present address: Viral Oncology Unit, Division of Medicine, Imperial College of Medicine, London W2 1PG, United Kingdom.

Molecular and Cellular Biology, November 1999, p. 7305-7313, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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