Zaire Ebola virus entry into human dendritic cells is insensitive to cathepsin L inhibition.
Cathepsins B and L contribute to Ebola virus (EBOV) entry into Vero cells and mouse embryonic fibroblasts. However, the role of cathepsins in EBOV-infection of human dendritic cells (DCs), important targets of infection in vivo, remains undefined. Here, EBOV-like particles containing a beta-lactamase-VP40 fusion reporter and Ebola virus were used to demonstrate the cathepsin dependence of EBOV entry into human monocyte-derived DCs. However, while DC infection is blocked by cathepsin B inhibitor, it is insensitive to cathepsin L inhibitor. Furthermore, DCs pre-treated for 48 h with TNFalpha were generally less susceptible to entry and infection by EBOV. This decrease in infection was associated with a decrease in cathepsin B activity. Thus, cathepsin L plays a minimal, if any, role in EBOV infection in human DCs. The inflammatory cytokine TNFalpha modulates cathepsin B activity and affects EBOV entry into and infection of human DCs.
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Osvaldo
O
Martinez
Joshua
J
Johnson
Balaji
B
Manicassamy
Lijun
L
Rong
Gene G
GG
Olinger
Lisa E
LE
Hensley
Christopher F
CF
Basler
D000818:Animals; D015153:Blotting, Western; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000502:physiology; D056668:Cathepsin L / Q000037:antagonists & inhibitors* / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000648:ultrastructure / Q000821:virology*; D004151:Dipeptides / Q000494:pharmacology; D029043:Ebolavirus / Q000502:physiology* / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014709:Vero Cells
C400541:CA 074 methyl ester; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002401:Cathepsin B; D056668:Cathepsin L