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J. Virol. doi:10.1128/JVI.00082-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Uniocular Anterior Chamber Inoculation of a TNF- Expressing Recombinant of HSV-1 Results in More Rapid Destruction and Increased Viral Replication in the Retina of the Uninoculated Eye

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

^* To whom correspondence should be addressed. Email: satherton{at}mail.mcg.edu.

	Abstract

TNF- has been shown to have a protective role in the eye and brain of HSV-1 infected mice. To determine whether overexpression of TNF- affected the course of virus infection following uniocular anterior chamber (AC) inoculation, a recombinant of HSV-1 (KOSTNF) was constructed that produces TNF- constitutively. BALB/c mice were injected with the TNF- recombinant, with a recombinant containing the pCI plasmid, with a recombinant rescue virus, or with the parental virus. Flow cytometry and immunohistochemistry were used to identify virus-infected cells and to determine the number and type of infiltrating inflammatory cells in the uninjected eye. The titer of virus was determined by plaque assay. There was no difference among all groups in virus titer or route and timing of virus spread in the injected eye or in the suprachiasmatic nuclei (SCN). However, in the uninjected eye of KOSTNF -infected mice, TNF- 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 titer of virus in the uninjected eye was significantly increased in KOSTNF-infected mice on day 7 p.i. compared with KOSpCI, KOS6rescue, or with KOS6 infected mice. The results suggest that instead of moderating infection and reducing virus spread, overexpression of TNF- has deleterious effects due to increased inflammation and virus infection resulting in earlier destruction of the retina of the uninoculated eye.