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Journal of Virology, February 2003, p. 2174-2181, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.2174-2181.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Virus Replication in Engineered Human Cells That Do Not Respond to Interferons

D. F. Young,1 L. Andrejeva,1 A. Livingstone,1 S. Goodbourn,2 R. A. Lamb,3 P. L. Collins,4 R. M. Elliott,5 and R. E. Randall1*

School of Biology, University of St. Andrews, Fife KY16 9TS,1 and Institute of Virology, University of Glasgow, Glasgow G11 5JR, Scotland,5 Department of Biochemistry and Immunology, St. George's Hospital Medical School, University of London, London SW17 0RE, England, United Kingdom,2 Howard Hughes Medical Institute and Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500,3 National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-80074

Received 19 August 2002/ Accepted 26 October 2002

The V protein of the paramyxovirus simian virus 5 blocks interferon (IFN) signaling by targeting STAT1 for proteasome-mediated degradation. Here we report on the isolation of human cell lines that express the V protein and can no longer respond to IFN. A variety of viruses, particularly slow-growing wild-type viruses and vaccine candidate viruses (which are attenuated due to mutations that affect virus replication, virus spread, or ability to circumvent the IFN response), form bigger plaques and grow to titers that are increased as much as 10- to 4,000-fold in these IFN-nonresponsive cells. We discuss the practical applications of using such cells in vaccine development and manufacture, virus diagnostics and isolation of newly emerging viruses, and studies on host cell tropism and pathogenesis.

* Corresponding author. Mailing address: School of Biomedical Sciences, University of St. Andrews, Biomolecular Sciences Bldg., North Haugh, St. Andrews, Fife, Scotland KY16 9TS, United Kingdom. Phone: 44 1334-462595. Fax: 44 1334-463397. E-mail: rer{at}st-and.ac.uk.

Journal of Virology, February 2003, p. 2174-2181, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.2174-2181.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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