The serine protease inhibitors, aprotinin and 6-amidino-2-naphthyl-p-guanidinobenzoate (Futhan), showed striking antiviral activity in the plaque assay of the canine kidney (MDCK) cell-WSN strain system. Anti-cathepsin B IgG antibody/showed the greatest inhibitory effect on plaque formation, followed by anti-factor X antibody and then anti-plasminogen antibody. Anti-cathepsin B antibody inhibited the proteolytic cleavage of haemagglutinin (HA). These results suggest that a serine protease-like enzyme and the other protein that binds to anti-cathepsin B antibody may be involved in the process of WSN HA cleavage on the membrane surface of MDCK cells.
References
1.
AkerstromB., and BjorckL. (1986) A physicochemical study of protein G, a molecule with unique immunoglobulin-binding properties. J Biol Chem261: 10240–10247.
2.
AoyamaT.InoY.OzakiM.OdaM.SatoT.KoshiyamaY.SuzukiS., and FujitaM. (1984) Pharmacological studies of FUT-175, nafamostat mesilate 1, inhibition of protease activity in vitro and in vivo experiments. J J Pharmacol35: 203–227.
3.
FlickD.A., and GiffordG.E. (1984) Comparison of in vitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods68: 167–175.
4.
FujiiS., and HitomiY. (1981) New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochem Biophys Acta661: 342–345.
5.
GartenW.BoshF.X.UnderD.RottR., and KlenkH.-D. (1981) Proteolytic activation of the influenza virus hemagglutinin; the structure of the cleavage site and the enzymes involved in cleavage. Virology115: 361–374.
6.
GartenW.StienekeA.ShawE.WikstromP., and KlenkH.-D. (1989) Inhibition of proteolytic activation of influenza virus hemagglutin by specific peptidyl chloroalkyl ketones. Virology172: 25–31.
7.
GotohB.OgasawaraT.ToyodaT.InocencioN.M.Hamagi-ChiM., and NagaiY. (1990) An endoprotease homologous to the blood clotting factor X as a determinant of viral tropism in chick embryo. EMBO J9: 4189–4195.
8.
HuangR.T.C.WahnK.KlenkH.-D., and RottR. (1980) Fusion between cell membrane and liposomes containing the glycoproteins of influenza virus. Virology104: 294–302.
9.
IwakiM.InoY.MotoyoshiA.OzakiM.SatoT.KurumiM., and AoyamaT. (1986) Pharmacological studies of FUT-175, nafamostat mesilate V, effects on the pancreatic enzymes and experimental acute pancreatitis in rats. J J Pharmacol41: 155–162.
10.
LaemmliU.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227: 680–685.
11.
LaskeyR.A., and MillsA.D. (1975) Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem56: 335–341.
12.
LindmarkR.Thoren-TollingK., and SjoquistT. (1983) Binding of immunoglobulin levels in mammalian sera. J Immunol Methods62: 1–13.
13.
ManK.G.JennyR.S., and KrishnaswangS. (1988) Cofactor proteins in the assembly and expression of blood clotting enzyme complex. Ann Rev Biochem57: 915–956.
14.
SomeyaA.TanakaN., and OkuyamaA. (1990) Inhibition of influenza virus A/WSN replication by a trypsin inhibitor, 6-amidino-2-naphthyl p-guanidinobenzoate. Biochem Biophys Res Commun169: 148–152.
15.
Stieneke-GroberA.VeyM.AnglikerH.ShawE.ThomasG.RobertsC.KlenkH.-D., and GartenW. (1992) Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a substilisin-like endoprotease. EMBO J11: 2407–2414.
16.
SugiuraA.UedaM.TobitaK., and EnomotoC. (1975) Further isolation and characterization of temperature-sensitive mutants of influenza virus. Virology65: 363–373.
17.
TashiroM.KlenkH.-D., and RottR. (1987) Inhibitory effect of a protease inhibitor, leupeptin, on the development of influenza pneumonia, mediated by concomitant bacteria. J Gen Virol68: 2039–2041.
18.
WalkerJ.A., and KawaokaY. (1993) Importance of conserved amino acids at the cleavage site of the haemagglutinin of a virulent avian influenza A virus. J Gen Virol73: 311–314.
19.
WebsterR.G., and RottR. (1987) Influenza virus A pathogenicity; the pivotal role of hemagglutinin. Cell50: 665–666.
20.
ZhirnovO.P.OvcharenkoA.V., and BukrinskayaA.G. (1984) Suppression of influenza virus replication in infected mice by protease inhibitors. J Gen Virol74: 311–314.
