Cytomegalovirus Blocks Autophagy During Infection of the Retinal Pigment Epithelial Cells: Functional Relationship Between Autophagy and Apoptosis

Autophagy is involved in the pathogenesis of human cytomegalovirus infection. Our recent results suggest that murine cytomegalovirus (MCMV) might own a strategy to inhibit or block autophagy activity by targeting a later process of autophagy, such as formation of autolysosomes or degradation of their content in infected retinal pigment epithelial (RPE) cells. Although the levels of LC3B-II were consistently increased during MCMV infection of RPE cells, administration of chloroquine or ammonium chloride increased LC3B-II expression only at the early stage of infection [6 h postinoculation (p.i.) and 12 h p.i.], but not at or after 24 h p.i. By counting punctate autophagic vacuoles in GFP-LC3 transfected RPE cells or by electron microscopy (EM) examination, the number of autophagic vacuoles was significantly increased in MCMV-infected RPE cells compared to uninfected controls. Compared to untreated MCMV-infected control cells, rapamycin treatment resulted in a significant decrease in the levels of cleaved caspase 3 as well as a significant decrease in the ratio of phosphorylated mTOR to total mTOR and in the ratio of phosphorylated P70S6K to total P70S6K. In addition, rapamycin-induced autophagy decreases caspase 3-dependent apoptosis during MCMV retinitis. It is suggested that there is a functional relationship between autophagy and apoptosis, which plays an important role during MCMV ocular infection.