Immune cell infiltration in corneas of mice with recurrent herpes simplex virus disease. – PubMed

Immune cell infiltration in corneas of mice with recurrent herpes simplex virus disease. - PubMed

Immune cell infiltration in corneas of mice with recurrent herpes simplex virus disease. - PubMed
The spread of herpes simplex virus (HSV) through neural tissues was studied in three inbred mouse strains that differ in susceptibility to HSV stromal keratitis. Toxicity was assessed using a dye reduction assay. Then, we investigated the efficacy of LL-37 peptides delivered through nanoparticles incorporated within the corneal implants to block HSV-1 viral activity. This work has clearly shown that stromal keratitis is an immunopathological disease, most likely due to the induction of a delayed type hypersensitivity response. Local administration of IL-10 also dramatically reduced the number of T cells and neutrophils migrating into the cornea and suppressed the severity of corneal disease. The immune modulatory role of IDO1 was analysed to determine whether IDO1 might contribute to modulating the recall responses of HSV-1-sensitised CD4(+) T cells. Future therapies aimed to increase the production and activity of sVR-1 protein could benefit the management of stromal keratitis, an important cause of human blindness.

In the first two specific aims of this proposal, we will characterize the role that ICP27 plays in restricting productive infection and promoting viral latency, using ICP27 null mutants, an ICP27 promoter mutant with delayed kinetics of expression, and viral mutants with deletions in different ICP27 functional domains. Tolerance was restricted to DTH, as antibodies to HSV antigens could be readily demonstrated 6-7 days after intravenous virus immunization. These findings demonstrate that viral infection of periocular tissue and subsequent disease development occurs by zosteriform spread from the cornea to the periocular tissue via the trigeminal ganglion rather than by direct spread from cornea to the periocular skin. By day 92 p.i., the inflammatory infiltrate diminished but was heaviest in mice with active periocular skin disease. The high proportion of CD8+ cells in epithelial disease compared with stromal disease suggests that they may be acting as suppressors.

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