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Partha S. Bhattacharjee, Tashfin S. Huq, Doan Thuy, Kaur Jaspreet, Joannie M. Ivory, Valencia Potter, Christina S. Simmons, Christian Clement, Harris E. McFerrin, Jr., James M. Hill; Effect Of Human Apolipoprotein E Genotype On The Ocular Recurrence Of Herpes Simplex Virus Type 1 Infection In Latent Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1483.
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Herpetic stromal keratitis (HSK) is an eye disease caused by herpes simplex virus type 1 (HSV-1).A significant percentage of patients receiving intense therapy fail to respond. The virus can recur periodically and each recurrence can be more severe than previous ones. The recurrent HSK clinically recognized by neovascularization (new blood vessel sprouting) and opacity is chronic and more severe than acute HSK. We have reported that human apolipoprotein E (apoE) has allele-specific roles in the pathogenesis of acute HSV-1 infection in the mouse eyes (Exp. Eye. Res.87:122, 2008). Whether apoE has a similar role in the pathogenesis of recurrent HSK is unknown.
We focused on identifying the role of human apoE genotypes in the pathogenesis of recurrent HSK in mice. Transgenic mice deleted of mouse apoE (apoE-null), knocked-in for the human apoE isoform 3 (apoE3), or apoE isoform 4 (apoE4) and their parent C57Bl/6 mice, had corneal inoculation with the high reactivating HSV-1 strain McKrae. Five weeks after acute infection, mice with clear eyes negative for virus shedding were exposed to UV irradiation (UV-B) in their right eyes. Eyes were monitored for corneal opacity, neovascularization and viral replication.
At 3 and 5 days post-UV irradiation, HSV-1 shedding from apoE4 mice was significantly higher (p < 0.05) compared to apoE3. Time onset and severity of corneal pathology (opacity and neovascularization) in apoE4 mice were also significantly higher (p < 0.05) than apoE3 mice. Compared to C57Bl/6 mice, apoE-null mice had reduced viral shedding and corneal pathology, suggesting apoE is necessary for establishment and severity of recurrent HSK in mouse eyes.
This is the first report linking the isoform-specific role of human apoE in the recurrence of HSV-1 infection in mouse eyes.
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