This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pasieka, T. J.
Right arrow Articles by Leib, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pasieka, T. J.
Right arrow Articles by Leib, D. A.

 Previous Article  |  Next Article 

Journal of Virology, March 2009, p. 2075-2087, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.02007-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Host Responses to Wild-Type and Attenuated Herpes Simplex Virus Infection in the Absence of Stat1{triangledown} ,{ddagger}

Tracy Jo Pasieka,1,{dagger} Cristian Cilloniz,2,3,{dagger} Betty Lu,1 Thomas H. Teal,2,3 Sean C. Proll,2,3 Michael G. Katze,2,3 and David A. Leib1,4*

Departments of Ophthalmology and Visual Sciences,1 Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110,4 Department of Microbiology, University of Washington School of Medicine,2 Washington National Primate Research Center, Seattle, Washington 981953

Received 23 September 2008/ Accepted 12 December 2008

Humans and mice lacking the interferon signaling molecule Stat1 are sensitive to a variety of pathogens due to their presumed inability to mount a strong innate immune response. The herpes simplex virus type 1 (HSV-1) virion host shutoff (vhs) protein is a multifunctional immunomodulator that counteracts the innate immune response and viruses lacking vhs are attenuated and effective live vaccines in animal models. To investigate the interplay of viruses with an immunocompromised host, we performed functional genomics analyses on control and Stat1–/– mouse corneas infected with wild-type or vhs-null viruses. In control mice, correlative with viral growth, both viruses induced a transient increase in immunomodulators, followed by viral clearance. In contrast, infection of the Stat1–/– mice induced a heightened and prolonged induction of inflammatory modulators for both viruses, manifesting as a significant immune cell infiltrate and ocular disease. Moreover, while wild-type virus infection of Stat1–/– was always lethal, vhs-null infection was rarely lethal. There was a significant increase in Stat3- and interleukin-6 (IL-6)-dependent transcription in Stat1–/– mice, implicating the Stat3 and IL-6 pathways in the observed ocular pathology. Further, infected Stat1–/– mice showed phosphorylated Stat3 in the corneal epithelium. Our data show a role for vhs in evading innate host responses and a role for Stat1 in limiting virus infection and for facilitating an appropriate nonpathological inflammatory response.

* Corresponding author. Mailing address: Washington University School of Medicine, Department of Ophthalmology and Visual Sciences, 660 South Euclid Ave., Box 8096, St. Louis, MO 63110. Phone: (314) 362-2689. Fax: (314) 362-3638. E-mail: leib{at}vision.wustl.edu

{triangledown} Published ahead of print on 24 December 2008.

{ddagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} T.J.P. and C.C. contributed equally to this study.

Journal of Virology, March 2009, p. 2075-2087, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.02007-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»