Antiviral effects of glycosylation and glucose trimming inhibitors on human parainfluenza virus type 3.
Endoplasmic reticulum (ER) alpha-glucosidase inhibitors block the trimming of N-linked glycosylation and thus prevent the production of several viruses. The present study investigates the antiviral effects of the alpha-glucosidase and alpha-mannosidase inhibitors (castanospermine, 1-deoxynojirimycin, bromoconduritol, deoxymannojirimycin and swainsonine) on human parainfluenza virus type 3 (HPIV3). The alpha-glucosidase inhibitors (castanospermine, 1-deoxynojirimycin) in recombinant expression systems reduced the surface and intracellular expression of both HPIV3 F and HN proteins. On the other hand, alpha-mannosidase inhibitors prevented processing of the oligosaccharides on HPIV3 glycoproteins into the complex form. Consequently, alpha-glycosidase inhibitors (castanospermine and 1-deoxynojirimycin) significantly inhibited viral fusion activity. We demonstrated that the alpha-glucosidase inhibitors (castanospermine and 1-deoxynojirimycin) reduced the infectivity of newly released viral particles. We postulate that alpha-glucosidase inhibitors can prevent the first steps of HPIV3 envelope glycoprotein processing and that the inhibition of glucose trimming has antiviral effects.
Tanaka
Yoshikazu
Y
Department of Veterinary Hygiene, Veterinary School, Nippon Veterinary & Life Science University, 1-7-1 Kyounan, Musashino, Tokyo 180-8602, Japan. ytanaka@nvlu.ac.jp
Kato
Junko
J
Kohara
Michinori
M
Galinski
Mark S
MS
D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors; D006031:Glycosylation / Q000187:drug effects*; D015707:HN Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010224:Parainfluenza Virus 3, Human / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D000520:alpha-Glucosidases / Q000494:pharmacology*; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D015707:HN Protein; D011994:Recombinant Proteins; D014760:Viral Fusion Proteins; C072983:F protein, parainfluenza virus 3; D000520:alpha-Glucosidases; D043323:alpha-Mannosidase; D005947:Glucose