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Journal of Virology, January 2009, p. 1147-1151, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.00105-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mice Lacking the ISG15 E1 Enzyme UbE1L Demonstrate Increased Susceptibility to both Mouse-Adapted and Non-Mouse-Adapted Influenza B Virus Infection{triangledown}

Caroline Lai,1 Jessica J. Struckhoff,1 Jana Schneider,3 Luis Martinez-Sobrido,4,5 Thorsten Wolff,3 Adolfo García-Sastre,4,5,6 Dong-Er Zhang,7,{dagger} and Deborah J. Lenschow1,2*

Departments of Internal Medicine,1 Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri 63110,2 Robert Koch-Institute, P15, 13353 Berlin, Germany,3 Department of Microbiology,4 Division of Infectious Diseases, Department of Medicine,5 Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York 10029,6 The Scripps Research Institute, La Jolla, California7

Received 15 January 2008/ Accepted 24 October 2008

ISG15 functions as a critical antiviral molecule against influenza virus, with infection inducing both the conjugation of ISG15 to target proteins and production of free ISG15. Here, we report that mice lacking the ISG15 E1 enzyme UbE1L fail to form ISG15 conjugates. Both UbE1L–/– and ISG15–/– mice display increased susceptibility to influenza B virus infection, including non-mouse-adapted strains. Finally, we demonstrate that ISG15 controls influenza B virus infection through its action within radioresistant stromal cells and not bone marrow-derived cells. Thus, the conjugation of ISG15 to target proteins within stromal cells is critical to its activity against influenza virus.


* Corresponding author. Mailing address: Washington University School of Medicine, 660 S. Euclid Ave., Box 8045, St. Louis, MO 63110. Phone: (314) 362-8637. Fax: (314) 454-1091. E-mail: dlenscho{at}im.wustl.edu

{triangledown} Published ahead of print on 12 November 2008.

{dagger} Department of Pathology and Biological Sciences, University of California San Diego, Moores UCSD Cancer Center, La Jolla, CA 92093.


Journal of Virology, January 2009, p. 1147-1151, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.00105-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Hsiang, T.-Y., Zhao, C., Krug, R. M. (2009). Interferon-Induced ISG15 Conjugation Inhibits Influenza A Virus Gene Expression and Replication in Human Cells. J. Virol. 83: 5971-5977 [Abstract] [Full Text]