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Journal of Virology, December 2009, p. 12559-12568, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.00939-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Evasion of the Mucosal Innate Immune System by Herpes Simplex Virus Type 2 {triangledown}

Tao Peng,1,2 Jia Zhu,1,3 Alexis Klock,1,3 Khamsone Phasouk,1,3 Meei-Li Huang,1,3 David M. Koelle,1,2,3,5 Anna Wald,1,2,3,4 and Lawrence Corey1,2,3,4*

Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,1 Departments of Medicine,2 Laboratory Medicine,3 Epidemiology,4 Global Health, University of Washington, Seattle, Washington 981955

Received 12 May 2009/ Accepted 15 September 2009

Understanding the mechanisms by which herpes simplex virus (HSV) evades host immune defenses is critical to defining new approaches for therapy and prevention. We performed transcriptional analyses and immunocytochemistry on sequential biopsy specimens of lesional tissue from the acute through the posthealing phases of recurrent mucocutaneous HSV-2 infection. Histological analysis of these biopsy specimens during the acute stage revealed a massive infiltration of T cells, as well as monocytes/macrophages, a large amount of myeloid, and a small number of plasmacytoid dendritic cells, in the dermis of these lesional biopsy specimens. Type I interferon (IFN-β and IFN-{alpha}) was poorly expressed and gamma IFN (IFN-{gamma}) potently induced during time periods in which we detected abundant amounts of HSV-2 antigens and HSV-2 RNA. IFN-stimulated genes were also markedly upregulated, with expression patterns that more closely matched those in primary human fibroblasts treated by IFN-{gamma} than those in fibroblasts treated by IFN-β. Transcriptional arrays of the same lesional biopsy sites during healing and at 2 and 4 weeks posthealing revealed no HSV nucleic acids or antigen; however, there was persistent expression of IFN-{gamma}, with very low levels of IFN-β and IFN-{alpha}. The findings of extremely low levels of IFN-{alpha} and IFN-β, despite the presence of a large number of cells capable of synthesizing these substances, suggest a potent alteration in host defense during HSV-2 infection in vivo. HSV-2's blockade of the innate immune system's production of type I IFN may be a major factor in allowing the virus to break through host mucosal defenses.

* Corresponding author. Mailing address: FHCRC, Program in Infectious Diseases, University of Washington, 1100 Fairview Ave. North, D3-100, P.O. Box 19024, Seattle, WA 98109-1024. Phone: (206) 667-6702. Fax: (206) 667-4411. E-mail: lcorey{at}u.washington.edu

{triangledown} Published ahead of print on 30 September 2009.

Journal of Virology, December 2009, p. 12559-12568, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.00939-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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