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Journal of Virology, January 2000, p. 564-572, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

alpha -Glucosidase Inhibitors Reduce Dengue Virus Production by Affecting the Initial Steps of Virion Morphogenesis in the Endoplasmic Reticulum

Marie-Pierre Courageot,1 Marie-Pascale Frenkiel,1 Claudia Duarte Dos Santos,2 Vincent Deubel,1 and Philippe Desprès1,*

Unité des Arbovirus et Virus des Fièvres Hémorragiques, Institut Pasteur, 75724 Paris, France,1 and Departamento Bioquimica e Biologia Molecular, Instituto Oswaldo Cruz, 21045-900 Rio de Janeiro, Rio de Janeiro, Brazil2

Received 19 July 1999/Accepted 29 September 1999

We report that endoplasmic reticulum alpha -glucosidase inhibitors have antiviral effects on dengue (DEN) virus. We found that glucosidase inhibition strongly affects productive folding pathways of the envelope glycoproteins prM (the intracellular glycosylated precursor of M [membrane protein]) and E (envelope protein): the proper folding of prM bearing unprocessed N-linked oligosaccharide is inefficient, and this causes delayed formation of prME heterodimer. The complexes formed between incompletely folded prM and E appear to be unstable, leading to a nonproductive pathway. Inhibition of alpha -glucosidase-mediated N-linked oligosaccharide trimming may thus prevent the assembly of DEN virus by affecting the early stages of envelope glycoprotein processing.

* Corresponding author. Mailing address: Unité des Arbovirus et Virus des Fièvres Hémorragiques, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris, France. Phone: 33 1 40613563. Fax: 33 1 40613774. E-mail: pdespres{at}pasteur.fr.

Journal of Virology, January 2000, p. 564-572, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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