This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fields, M. A.
Right arrow Articles by Atherton, S. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fields, M. A.
Right arrow Articles by Atherton, S. S.

 Previous Article  |  Next Article 

Journal of Virology, May 2008, p. 5068-5078, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.00082-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Uniocular Anterior Chamber Inoculation of a Tumor Necrosis Factor Alpha-Expressing Recombinant of Herpes Simplex Virus Type 1 Results in More Rapid Destruction and Increased Viral Replication in the Retina of the Uninoculated Eye{triangledown}

Mark A. Fields, Mei Zheng, Pam Wall, Scott Oberg, and Sally S. Atherton*

Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912

Received 13 January 2008/ Accepted 27 February 2008

Tumor necrosis factor alpha (TNF-{alpha}) has been shown to have a protective role in the eyes and brains of herpes simplex virus type 1 (HSV-1)-infected mice. To determine whether overexpression of TNF-{alpha} affected the course of virus infection following uniocular anterior chamber inoculation, a recombinant of HSV-1 that produces TNF-{alpha} constitutively (KOSTNF) was constructed. BALB/c mice were injected with the TNF-{alpha} recombinant, a recombinant containing the pCI plasmid, a recombinant rescue virus, or the parental virus. Flow cytometry and immunohistochemistry were used to identify virus-infected cells and to determine the numbers and types of infiltrating inflammatory cells in the uninjected eyes. Virus titers were determined by plaque assay. There were no differences among the groups in virus titers or the route and timing of virus spread in the injected eyes or in the suprachiasmatic nuclei. However, in the uninjected eyes of KOSTNF-infected mice, TNF-{alpha} expression was increased and there were more viral antigen-positive cells and immune inflammatory cells. There was earlier microscopic evidence of retinal infection and destruction in these mice, and the titers of virus in the uninjected eyes were significantly increased in KOSTNF-infected mice on day 7 postinfection compared with those of KOSpCI-, KOS6βrescue-, or KOS6β-infected mice. The results suggest that instead of moderating infection and reducing virus spread, overexpression of TNF-{alpha} has deleterious effects due to increased inflammation and virus infection that result in earlier destruction of the retina of the uninoculated eye.

* Corresponding author. Mailing address: Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912. Phone: (706) 721-3731. Fax: (706) 721-6120. E-mail: satherton{at}mail.mcg.edu

{triangledown} Published ahead of print on 5 March 2008.

Journal of Virology, May 2008, p. 5068-5078, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.00082-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shukla, S. Y., Singh, Y. K., Shukla, D. (2009). Role of Nectin-1, HVEM, and PILR-{alpha} in HSV-2 Entry into Human Retinal Pigment Epithelial Cells. IOVS 50: 2878-2887 [Abstract] [Full Text]  


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