1. MG-132 interferes with iron cellular homeostasis and alters virulence of bovine herpesvirus 1
- Author
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Luisa De Martino, Gian Carlo Tenore, Roberto Ciampaglia, Francesca Paola Nocera, Maria Grazia Ferraro, Carlo Irace, Filomena Fiorito, Rita Santamaria, Marialuisa Piccolo, Fiorito, F, Irace, C, Nocera, Fp, Piccolo, M, Ferraro, Mg, Ciampaglia, R, Tenore, Gc, Santamaria, R, and De Martino, L.
- Subjects
Programmed cell death ,Leupeptins ,040301 veterinary sciences ,Cellular homeostasis ,Transferrin receptor ,Virus Replication ,Cell Line ,0403 veterinary science ,03 medical and health sciences ,chemistry.chemical_compound ,Western blot ,medicine ,Animals ,Homeostasis ,Herpesvirus 1, Bovine ,030304 developmental biology ,0303 health sciences ,Virulence ,General Veterinary ,biology ,medicine.diagnostic_test ,Chemistry ,Acridine orange ,04 agricultural and veterinary sciences ,biology.organism_classification ,Bovine herpesvirus 1 ,Cell biology ,Ferritin ,Proteasome inhibitor ,biology.protein ,Cattle ,medicine.drug - Abstract
Bovine herpesvirus 1 (BoHV-1) requires an iron-replete cell host to replicate efficiently. BoHV-1 infection provokes an increase in ferritin levels and a decrease of transferrin receptor 1 (TfR-1) expression, ultimately lowering iron pool extent. Thus, cells try to limit iron availability for virus spread. It has been demonstrated that MG-132, a proteasome inhibitor, reduces BoHV-1 release. Since ferritin, the major iron storage protein in mammalian cells, undergoes proteasome-mediated degradation, herein, the influence of MG-132 on iron metabolism during BoHV-1 infection was examined. Following infection in bovine cells (MDBK), MG-132 reduced cell death and viral yield. Western blot analysis showed a significant ferritin accumulation, likely due to the inhibition of its proteasome-mediated degradation pathway. In addition, the concomitant down-regulation of TfR-1 expression, observed during infection, was counteracted by proteasome inhibitor. This trend may be explained by enhanced acidic vesicular organelles, detected by acridine orange staining, determining a reduction of intracellular pH, that promotes new synthesis of TfR-1 degraded in a recycling pathway. In addition, MG-132 influences cellular iron distribution during BoHV-1 infection, as revealed by Perls' Prussian blue staining. However, cellular iron content, evaluated by Atomic Absorption Spectrophotometry, resulted essentially unaltered. These findings reveal that MG-132 may contribute to limit cellular iron availability for virus replication thereby enhancing cell survival.
- Published
- 2021