Abstract
Recently it has been reported that a cathepsin B inhibitor, CA-074Me, attenuates ecotropic murine leukemia virus (Eco-MLV) infection in NIH3T3 cells, suggesting that cathepsin B is required for the Eco-MLV infection. However, cathepsin B activity was negative or extremely low in NIH3T3 cells. How did CA-074Me attenuate the Eco-MLV infection? The CA-074Me treatment of NIH3T3 cells inhibited cathepsin L activity, and a cathepsin L specific inhibitor, CLIK148, attenuated the Eco-MLV vector infection. These results indicate that the suppression of cathepsin L activity by CA-074Me induces the inhibition of Eco-MLV infection, suggesting that cathepsin L is required for the Eco-MLV infection in NIH3T3 cells. The CA-074Me treatment inhibited the Eco-MLV infection in human cells expressing the exogenous mouse ecotropic receptor and endogenous cathepsins B and L, but the CLIK148 treatment did not, showing that only the cathepsin L suppression by CLIK148 is not enough to prevent the Eco-MLV infection in cells expressing both of cathepsins B and L, and CA-074Me inhibits the Eco-MLV infection by suppressing both of cathepsins B and L. These results suggest that either cathepsin B or L is sufficient for the Eco-MLV infection.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Base Sequence
-
Cathepsin B / antagonists & inhibitors
-
Cathepsin B / genetics
-
Cathepsin B / physiology
-
Cathepsin L / antagonists & inhibitors
-
Cathepsin L / physiology*
-
Cell Line
-
Cysteine Proteinase Inhibitors / pharmacology
-
Dipeptides / pharmacology
-
Epoxy Compounds / pharmacology
-
Host-Pathogen Interactions / drug effects
-
Host-Pathogen Interactions / genetics
-
Host-Pathogen Interactions / physiology
-
Humans
-
Leukemia Virus, Murine / drug effects
-
Leukemia Virus, Murine / enzymology*
-
Leukemia Virus, Murine / pathogenicity
-
Leukemia, Experimental / etiology
-
Leukemia, Experimental / prevention & control
-
Membrane Glycoproteins / genetics
-
Membrane Glycoproteins / physiology
-
Mice
-
NIH 3T3 Cells
-
Pyridines / pharmacology
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Rats
-
Receptors, Virus / genetics
-
Receptors, Virus / physiology
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
Retroviridae Infections / etiology
-
Retroviridae Infections / prevention & control
-
Tumor Virus Infections / etiology
-
Tumor Virus Infections / prevention & control
Substances
-
CA 074 methyl ester
-
CLIK 148
-
Cysteine Proteinase Inhibitors
-
Dipeptides
-
Epoxy Compounds
-
Membrane Glycoproteins
-
Pyridines
-
RNA, Messenger
-
Receptors, Virus
-
Recombinant Proteins
-
ecotropic murine leukemia virus receptor
-
Cathepsin B
-
Ctsb protein, mouse
-
Cathepsin L
-
Ctsl protein, mouse