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

Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912, USA.
Journal of Virology (Impact Factor: 4.44). 06/2008; 82(10):5068-78. DOI: 10.1128/JVI.00082-08
Source: PubMed


Tumor necrosis factor alpha (TNF-α) 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-α affected the course of virus infection following
uniocular anterior chamber inoculation, a recombinant of HSV-1 that produces TNF-α constitutively (KOSTNF) was constructed. BALB/c mice were injected with the TNF-α 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-α 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-α
has deleterious effects due to increased inflammation and virus infection that result in earlier destruction of the retina
of the uninoculated eye.

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Available from: Sally S Atherton, Jan 15, 2015
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    • "TNF-a also produced a significant benefit when administered up to 8 h after the infection in a lethal mouse model of HSE (Rossol-Voth et al., 1991). However, an over-expression of TNF-a constitutively produced by a recombinant HSV-1 strain inoculated in the eye had deleterious effects due to increased inflammation and viral replication (Fields et al., 2008). High levels of TNF-a were also shown to induce blood–brain barrier (BBB) disruption (Candelario-Jalil et al., 2007). "
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