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Vol. 55, No. 6, 2012
Issue release date: October 2012
Section title: Original Paper
Intervirology 2012;55:451–464
(DOI:10.1159/000335262)

Inhibiting Rotavirus Infection by Membrane-Impermeant Thiol/Disulfide Exchange Blockers and Antibodies against Protein Disulfide Isomerase

Calderon M.N. · Guerrero C.A. · Acosta O. · Lopez S. · Arias C.F.
aChemistry Department, Science Faculty, and bPhysiological Science Department, Faculty of Medicine/Biotechnology Institute, Universidad Nacional de Colombia, Bogotá, Colombia; cBiotechnology Institute, Universidad Nacional Autonoma de Mexico, Cuernavaca, Mexico

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 11/23/2010
Accepted: 11/21/2011
Published online: 3/7/2012

Number of Print Pages: 14
Number of Figures: 8
Number of Tables: 0

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT

Abstract

Objectives: Determining the effect of membrane-impermeant thiol/disulfide exchange inhibitors on rhesus rotavirus infectivity in MA104 cells and investigating protein disulfide isomerase (PDI) as a potential target for these inhibitors. Methods: Cells were treated with DTNB [5,5-dithio-bis-(2-nitrobenzoic acid)], bacitracin or anti-PDI antibodies and then infected with virus. Triple-layered particles (TLPs) were also pretreated with inhibitors before inoculation. The effects of these inhibitors on α-sarcin co-entry, virus binding to cells and PDI-TLP interaction were also examined. FACS analysis, cell-surface protein biotin-labeling, lipid-raft isolation and ELISA were performed to determine cell-surface PDI expression. Results: Infectivity became reduced by 50% when cells or TLPs were treated with 1 or 6 mM DTNB, respectively; infectivity became reduced by 50% by 20 mM bacitracin treatment of cells whereas TLPs were insensitive to bacitracin treatment; anti-PDI antibodies decreased viral infectivity by about 45%. The presence of DTNB (2.5 mM) or bacitracin (20 mM) was unable to prevent virus binding to cells and rotavirus-induced α-sarcin co-entry. Conclusions: It was concluded that thiol/disulfide exchange was involved in rotavirus entry process and that cell-surface PDI was at least a potential target for DTNB and bacitracin-induced infectivity inhibition.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 11/23/2010
Accepted: 11/21/2011
Published online: 3/7/2012

Number of Print Pages: 14
Number of Figures: 8
Number of Tables: 0

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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