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M. Itahashi, D. M. Neumann, P. Bhattacharjee, J. M. Hill; Effect of Administering HSV-1 Antibody on the Establishment of Latency and Induced Reactivation in the Mouse Eye Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2668.
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To determine the optimal conditions under which HSV-1 reactivation can be induced in the mouse ocular model, we investigated the effect of rabbit anti-HSV-1 antibody (Ab) dosage on viral load in the trigeminal ganglia (TG) of HSV-1 latently infected mice followed by a combination of immunosuppression and heat stress.
Mice were divided into four groups: Group A received I.P. Ab at titer 1/640, B and D received Ab at titer 1/320, and C received no Ab. Titers were determined by neutralization assays. Corneas were inoculated with HSV-1; groups A, B, and C received strain McKrae (A and B=5 x 105 PFU/eye, C=6.25 x 103 PFU/eye), and group D received strain ΔLAT-2903 (5 x 105 PFU/eye). Herpetic keratitis was quantified by slit lamp examination (SLE). Corneal lesions were scored in a masked fashion and were analyzed based on the area under the curve (AUC). After latency was established in the TG, HSV-1 reactivation was induced by treating half of each group with cyclophosphamide and dexamethasone (immunosuppression) and heat stress. The other half of the mice in each group served as controls. Eye swabs were used to assay for the presence of infectious virus in eyes. Viral genome copy numbers in the TG were evaluated by quantitative PCR.
In all groups, there was no difference in the SLE scores or AUC. After treatment of latent mice, the virus positive eye swabs in McKrae groups A, B, and C were 47.6%, 51.9%, and 21.4%, respectively. In the ΔLAT2903 group (D), 11.1% of eye swabs were positive. Eye swabs from the controls (untreated, latent) were all negative. HSV-1 DNA copy numbers in group B (treated group, Ab titer 1/320) were significantly higher than in the untreated group. Groups receiving Ab had higher survival rates than groups receiving no Ab.
Antibody at the titer of 1/320 was found to be the most favorable condition in the mouse model for high HSV-1 reactivation in the McKrae group. Although the ΔLAT2903 had low induced reactivation, the HSV-1 copy numbers were not different from the McKrae group.
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