Inhibition of glycoprotein oligosaccharide processing in vitro and in influenza-virus-infected cells by alpha-D-mannopyranosylmethyl-p-nitrophenyltriazene

• Published in: Biochemical journal Vol. 255; no. 3; pp. 991 - 998
• Main Authors: McDowell, W, Tlusty, A, Rott, R, BeMiller, J N, Bohn, J A, Meyers, R W, Schwarz, R T
• Format: Journal Article
• Language: English
• Published: England 01-11-1988
• Subjects: alpha-Mannosidase; Animals; Chick Embryo; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Fabaceae - drug effects; Fabaceae - enzymology; Glycoproteins - metabolism; Golgi Apparatus - drug effects; Golgi Apparatus - enzymology; Influenza A virus - physiology; influenza virus; Liver - drug effects; Liver - enzymology; Mannans - metabolism; Mannosidases - antagonists & inhibitors; Oligosaccharides - metabolism; Plants, Medicinal; Rats; Triazenes - pharmacology
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2550991

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.