bafilomycin-a1 and Keratitis--Herpetic

Autophagy and apoptosis function as important early cellular defense mechanisms in infections and other diseases. The outcome of an infection is determined by a complex interplay between the pathogenic microorganism and these intracellular pathways. To better understand the cytopathogenicity of Herpes simplex virus types 1 and 2 (HSV-1 and - 2), we studied the effect of these viruses on the autophagic and apoptotic processes in the SIRC corneal cell line. Infection with the KOS strain of HSV-1 and a wild-type strain of HSV-2 enhanced autophagosome formation, triggered cytoplasmic acidification, increased LC3B lipidation and elevated the ratio of apoptotic cells. The autophagy inhibitor bafilomycin A1 triggered a significant increase in the apoptotic responses of HSV-1 and HSV-2-infected cells. Thus, both HSV types affect autophagy and apoptosis in a coordinated fashion, and autophagy plays cytoprotective role in HSV-infected cells via antagonizing apoptosis. Together these data implicate autophagy in the pathogenic mechanism of herpetic keratitis.

Topics: Acridine Orange; Analysis of Variance; Animals; Annexin A5; Apoptosis; Autophagy; Blotting, Western; Cell Line; Cornea; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Herpesvirus 1, Human; Herpesvirus 2, Human; Keratitis, Herpetic; Macrolides; Propidium; Rabbits