Cathepsin L is required for ecotropic murine leukemia virus infection in NIH3T3 cells.
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.
Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Hiroaki
H
Yoshii
Haruka
H
Kamiyama
Kazuo
K
Minematsu
Kensuke
K
Goto
Tsutomu
T
Mizota
Kazunori
K
Oishi
Nobuhiko
N
Katunuma
Naoki
N
Yamamoto
Yoshinao
Y
Kubo
D000818:Animals; D001483:Base Sequence; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D056668:Cathepsin L / Q000037:antagonists & inhibitors / Q000502:physiology*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D007942:Leukemia, Experimental / Q000209:etiology / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012192:Retroviridae Infections / Q000209:etiology / Q000517:prevention & control; D014412:Tumor Virus Infections / Q000209:etiology / Q000517:prevention & control
C400541:CA 074 methyl ester; C402823:CLIK 148; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D004852:Epoxy Compounds; D008562:Membrane Glycoproteins; D011725:Pyridines; D012333:RNA, Messenger; D011991:Receptors, Virus; D011994:Recombinant Proteins; C070506:ecotropic murine leukemia virus receptor; D002401:Cathepsin B; C533915:Ctsb protein, mouse; D056668:Cathepsin L; C534278:Ctsl protein, mouse