Cathepsin L is required for ecotropic murine leukemia virus infection in NIH3T3 cells.

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.

• Authors: Hiroaki Yoshii, Haruka Kamiyama, Kazuo Minematsu, Kensuke Goto, Tsutomu Mizota, Kazunori Oishi, Nobuhiko Katunuma, Naoki Yamamoto, Yoshinao Kubo
• Journal: Virology (Virology) Vol. 394 Issue 2 Pg. 227-34 (Nov 25 2009) ISSN: 1096-0341 [Electronic] United States
• PMID: 19781728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Animals
• Base Sequence
• Cathepsin B (antagonists & inhibitors, genetics, physiology)
• Cathepsin L (antagonists & inhibitors, physiology)
• Cell Line
• Cysteine Proteinase Inhibitors (pharmacology)
• Dipeptides (pharmacology)
• Epoxy Compounds (pharmacology)
• Host-Pathogen Interactions (drug effects, genetics, physiology)
• Humans
• Leukemia Virus, Murine (drug effects, enzymology, pathogenicity)
• Leukemia, Experimental (etiology, prevention & control)
• Membrane Glycoproteins (genetics, physiology)
• Mice
• NIH 3T3 Cells
• Pyridines (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Rats
• Receptors, Virus (genetics, physiology)
• Recombinant Proteins (genetics, metabolism)
• Retroviridae Infections (etiology, prevention & control)
• Tumor Virus Infections (etiology, prevention & control)