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  • Original Paper
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Anti-apoptotic and oncogenic properties of the dsRNA-binding protein of vaccinia virus, E3L

Oncogene volume 21, pages 8379–8387 (2002)Cite this article

Abstract

The vaccinia virus (VV) E3L gene encodes a dsRNA binding protein that inhibits activation of the IFN-induced, dsRNA-dependent protein kinase, (PKR), the 2–5A synthetases/RNase L system and other dsRNA dependent pathways, thus leading to efficient VV replication. To analyse E3L effects over cellular metabolism in a virus-free system, we have generated stable mouse 3T3 cell lines expressing E3L. Expression of E3L in NIH3T3 cells results in inhibition of eIF-2α phosphorylation and IκBα degradation in response to dsRNA. Antiviral responses induced by IFN-α/β were partially impaired in 3T3-E3L cells, as determined by a viability assay upon VSV infection. E3L expression also confers resistance to dsRNA-triggered apoptosis. Interestingly, cells expressing E3L grew faster than control cells, and showed increased expression of cyclin A and decreased levels of p27Kip1. E3L cooperated with H-ras in a focus formation assay, and NIH3T3 E3L cells formed solid tumors when injected in nude mice. Overall, our findings reveal that interference of E3L protein with several cellular pathways, results in promotion of cellular growth, impairment of antiviral activity and resistance to apoptosis.

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Acknowledgements

We recognize Bertram L Jacobs (Arizona State University, AZ, USA) for the generous gift of the E3L antibody. We are grateful to Marcos Malumbres and Rocio Sotillo for helpful comments on transformation assays. We thank Don Roth for revision of the manuscript. This investigation was supported by research grants BIO2001-2269 of Spain and EU (BIO4-CT98-0456). MA García and J Gil were supported by fellowships from Ministerio de Ciencia y Tecnología, Spain.

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  1. Jesús Gil

    Present address: Wolfson Institute for Biomedical Research, University College of London, Gower Street, London, WC1E 6BT, UK

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, (CSIC), Campus Universidad Autónoma, Madrid, 28049, Spain

    Maria Angel García, Susana Guerra, Jesús Gil, Victoria Jimenez & Mariano Esteban

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  1. Maria Angel García
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Correspondence to Mariano Esteban.

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García, M., Guerra, S., Gil, J. et al. Anti-apoptotic and oncogenic properties of the dsRNA-binding protein of vaccinia virus, E3L. Oncogene 21, 8379–8387 (2002). https://doi.org/10.1038/sj.onc.1206036

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