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Journal of Virology, July 2001, p. 6204-6208, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6204-6208.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Role of the Promyelocytic Leukemia Protein PML in the Interferon Sensitivity of Lymphocytic Choriomeningitis Virus

Mahmoud Djavani,1 Juan Rodas,1 Igor S. Lukashevich,1 Douglas Horejsh,1 Pier Paolo Pandolfi,2 Katherine L. B. Borden,3 and Maria S. Salvato1,*

Institute of Human Virology, University of Maryland Biotechnology Center, Baltimore, Maryland 212011; Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 100212; and Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029-65743

Received 22 December 2000/Accepted 23 March 2001

Lymphocytic choriomeningitis virus (LCMV) induces type I interferon (alpha and beta interferon [IFN-alpha and IFN-beta ]) upon infection and yet is sensitive to the addition of type II interferon (gamma interferon [IFN-gamma ]) to the culture media. This sensitivity is biologically important because it correlates inversely with the ability of certain LCMV strains to persist in mice (D. Moskophidis, M. Battegay, M. A. Bruendler, E. Laine, I. Gresser, and R. M. Zinkernagel, J. Virol. 68:1951-1955, 1994). The cellular oncoprotein PML is induced by both IFN-alpha /beta and IFN-gamma , and PML binds the LCMV Z protein and becomes redistributed within cells from nucleus to cytoplasm upon LCMV infection. In the present study, increased PML expression results in diminished LCMV replication, implicating PML in the IFN sensitivity of LCMV. Virus production in PML -/- murine embryonic fibroblasts (MEF) exceeds virus production in PML +/+ MEF, and this difference is exacerbated by IFN treatment that upregulates PML expression. IFN-gamma also diminishes LCMV production in PML -/- cells; therefore, viral IFN sensitivity is not entirely due to PML. Both viral mRNA production and viral protein production decrease as PML expression increases. Here we propose that PML reduces LCMV transcription through its interaction with the Z protein.

* Corresponding author. Mailing address: Institute of Human Virology, University of Maryland Biotechnology Center, 725 W. Lombard St., Baltimore, MD 21201. Phone: (410) 706-1368. Fax: (410) 706-1992. E-mail: salvato{at}umbi.umd.edu.

Journal of Virology, July 2001, p. 6204-6208, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6204-6208.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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