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PMID: 2825177 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of human immunodeficiency virus syncytium formation and virus replication by castanospermine.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 84 ·No. 22 ·1987-11-00 ·Pages 8120-4

Walker BD, Kowalski M, Goh WC, Kozarsky K, Krieger M, Rosen C, Rohrschneider L, Haseltine WA, Sodroski J

Abstract

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) is a plant alkaloid that modifies glycosylation by inhibiting alpha-glucosidase I. Castanospermine is shown to inhibit syncytium formation induced by the envelope glycoprotein of the human immunodeficiency virus and to inhibit viral replication. The decrease in syncytium formation in the presence of castanospermine can be attributed to inhibition of processing of the envelope precursor protein gp160, with resultant decreased cell surface expression of the mature envelope glycoprotein gp120. In addition, castanospermine may cause defects in steps involved in membrane fusion after binding of CD4 antigen. The antiviral effects of castanospermine may be due to modifications of the envelope glycoprotein that affect the ability of the virus to enter cells after attachment to the CD4 cell receptor.

MeSH Terms
Alkaloids/pharmacology Animals Antigens, Differentiation, T-Lymphocyte/metabolism Cell Fusion/drug effects Cell Line Cricetinae Cricetulus Female Fibroblasts Glycoside Hydrolase Inhibitors HIV/drug effects,physiology HIV Envelope Protein gp120 Humans Indolizines Lymphocytes/physiology Ovary Protein Precursors/metabolism Protein Processing, Post-Translational/drug effects Receptors, Virus/metabolism Retroviridae Proteins/biosynthesis,physiology Tumor Cells, Cultured Virus Replication/drug effects
Chemicals
Alkaloids Antigens, Differentiation, T-Lymphocyte Glycoside Hydrolase Inhibitors HIV Envelope Protein gp120 Indolizines Protein Precursors Receptors, Virus Retroviridae Proteins castanospermine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Walker B D
Infectious Disease Unit, Massachusetts General Hospital, Boston.
Kowalski M
Goh W C
Kozarsky K
Krieger M
Rosen C
Rohrschneider L
Haseltine W A
Sodroski J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.84.22.8120
Published
1987-11-00
Pages
8120-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC299490
Subset
IM
Grants
NCI NIH HHS · CA28151 · United States
NCI NIH HHS · CA40658 · United States
NCI NIH HHS · CA40987 · United States
External Links
PubMed source DOI: 10.1073/pnas.84.22.8120 PMC Full Text View journal details
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