Inhibition of human immunodeficiency virus syncytium formation and virus replication by castanospermine.
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.
Walker
B D
BD
Infectious Disease Unit, Massachusetts General Hospital, Boston.
Kowalski
M
M
Goh
W C
WC
Kozarsky
K
K
Krieger
M
M
Rosen
C
C
Rohrschneider
L
L
Haseltine
W A
WA
Sodroski
J
J
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002459:Cell Fusion / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005347:Fibroblasts; D065089:Glycoside Hydrolase Inhibitors; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015699:HIV Envelope Protein gp120; D006801:Humans; D007212:Indolizines; D008214:Lymphocytes / Q000502:physiology; D010053:Ovary; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011991:Receptors, Virus / Q000378:metabolism; D012191:Retroviridae Proteins / Q000096:biosynthesis* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*; D054836:Indolizidines
D000470:Alkaloids; D000945:Antigens, Differentiation, T-Lymphocyte; D065089:Glycoside Hydrolase Inhibitors; D015699:HIV Envelope Protein gp120; D007212:Indolizines; D011498:Protein Precursors; D011991:Receptors, Virus; D012191:Retroviridae Proteins; C037806:castanospermine; D054836:Indolizidines