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Journal of Virology, December 2009, p. 12399-12406, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.00888-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Control of Herpes Simplex Virus Replication Is Mediated through an Interferon Regulatory Factor 3-Dependent Pathway{triangledown}

Vineet D. Menachery1,3 and David A. Leib1,2*

Departments of Ophthalmology and Visual Sciences,1 Molecular Microbiology,2 Program in Immunology, Washington University School of Medicine, St. Louis, Missouri, 631103

Received 2 May 2009/ Accepted 8 September 2009

The type I interferon (IFN) cascade is critical in controlling viral replication and pathogenesis. Recognition pathways triggered by viral infection rapidly induce the type I IFN cascade, often in an IFN regulatory factor 3 (IRF-3)-dependent fashion. This dependence predicts that loss of IRF-3 would render early recognition pathways inoperative and thereby impact virus replication, but this has not been observed previously with herpes simplex virus type 1 (HSV-1) in vitro. In this study, HSV-1-infected IRF-3–/– bone marrow-derived dendritic cells (BMDCs) and macrophages supported increased HSV replication compared to control cells. In addition, IRF-3-deficient BMDCs exhibited delayed type I IFN synthesis compared to control cells. However, while IFN pretreatment of IRF-3–/– BMDCs resulted in reduced virus titers, a far greater reduction was seen after IFN treatment of wild-type cells. This suggests that even in the presence of exogenously supplied IFN, IRF-3–/– BMDCs are inherently defective in the control of HSV-1 replication. Together, these results demonstrate a critical role for IRF-3-mediated pathways in controlling HSV-1 replication in cells of the murine immune system.

* Corresponding author. Present address: Department of Microbiology and Immunology, Dartmouth-Hitchcock Medical Center, 630E Borwell Building, HB 7556, 1 Medical Center Dr., Lebanon, NH 03756. Phone: (603) 650-8616. Fax: (603) 650-6223. E-mail: david.a.leib{at}dartmouth.edu

{triangledown} Published ahead of print on 16 September 2009.

Journal of Virology, December 2009, p. 12399-12406, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.00888-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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