Inhibition of glycoprotein oligosaccharide processing in vitro and in influenza-virus-infected cells by alpha-D-mannopyranosylmethyl-p-nitrophenyltriazene.
The effects of alpha-D-mannopyranosylmethyl-p-nitrophenyltriazene (MMNT) on mannosidases involved in asparagine-linked oligosaccharide processing were investigated. MMNT was found to inhibit the activity of rat liver Golgi alpha-mannosidase I in a concentration-dependent manner (50% inhibition with 0.18 mM-MMNT), whereas rat liver endoplasmic-reticulum alpha-mannosidase appeared to be resistant (less than 5% inhibition at 1 mM-MMNT). Jack-bean alpha-mannosidase was also sensitive to inhibition by MMNT (50% inhibition with 0.32 mM-MMNT). Treatment of influenza-virus-infected chick-embryo cells with 1 mM-MMNT led to a decrease in the formation of complex-type asparagine-linked oligosaccharides and an accumulation of high-mannose-type oligosaccharides with the composition Man8(GlcNAc)2 and Man7(GlcNAc)2 on the viral glycoproteins. The biological activities of influenza-virus haemagglutinin and neuraminidase synthesized in the presence of 1 mM-MMNT remained unchanged, but the virus was less infectious than the control.
McDowell
W
W
Institut für Virològie, Justus Liebig Universität Giessen, Federal Republic of Germany.
Tlusty
A
A
Rott
R
R
BeMiller
J N
JN
Bohn
J A
JA
Meyers
R W
RW
Schwarz
R T
RT
D000818:Animals; D002642:Chick Embryo; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D007887:Fabaceae / Q000187:drug effects / Q000201:enzymology; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects / Q000201:enzymology; D009980:Influenza A virus / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008351:Mannans / Q000378:metabolism; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D009844:Oligosaccharides / Q000378:metabolism*; D010946:Plants, Medicinal; D051381:Rats; D014226:Triazenes / Q000494:pharmacology*; D043323:alpha-Mannosidase
D006023:Glycoproteins; D008351:Mannans; D009844:Oligosaccharides; D014226:Triazenes; C047982:mannopyranosylmethyl-4-nitrophenyltriazene; C057328:mannosyl(9)-N-acetylglucosamine; D008361:Mannosidases; D043323:alpha-Mannosidase