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Journal of Virology, October 2003, p. 11082-11093, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11082-11093.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Bioluminescence Imaging Reveals Systemic Dissemination of Herpes Simplex Virus Type 1 in the Absence of Interferon Receptors

Gary D. Luker,1* Julie L. Prior,1 Jiling Song,1 Christina M. Pica,1 and David A. Leib2

Molecular Imaging Center, Mallinckrodt Institute of Radiology,1 Departments of Ophthalmology and Visual Sciences and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 631102

Received 8 May 2003/ Accepted 21 July 2003

Herpes simplex virus type 1 (HSV-1) can produce disseminated, systemic infection in neonates and patients with AIDS or other immunocompromising diseases, resulting in significant morbidity and mortality in spite of antiviral therapy. Components of host immunity that normally limit HSV-1 to localized epithelial and neuronal infection remain incompletely defined. We used in vivo bioluminescence imaging to determine effects of type I and II interferons (IFNs) on replication and tropism of HSV-1 infection in mice with genetic deficiency of type I, type II, or both type I and II IFN receptors. Following footpad or ocular infection of mice lacking type I IFN receptors, HSV-1 spread to parenchymal organs, including lung, liver, spleen, and regional lymph nodes, but mice survived. Deletion of type I and II IFN receptors produced quantitatively greatest and most widespread dissemination of virus to visceral organs and the nervous system, and these mice invariably died after ocular or footpad infection. Type II receptor knockout and wild-type mice had comparable viral replication and localization, with no systemic spread of HSV-1 or lethality. Therefore, while isolated deficiency of type II IFN receptors did not affect pathogenesis, loss of these receptors in combination with genetic deletion of type I receptors had a profound effect on susceptibility to HSV-1. These data demonstrate different effects of type I and II IFNs in limiting systemic dissemination of HSV-1 and further validate the use of bioluminescence imaging for studies of viral pathogenesis.

* Corresponding author. Mailing address: Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Box 8225, 4525 Scott Ave., Room 3324, St. Louis, MO 63110. Phone: (314) 362-9359. Fax (314) 362-0152. E-mail: lukerg{at}mir.wustl.edu.

Journal of Virology, October 2003, p. 11082-11093, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11082-11093.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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