The alpha-glucosidase inhibitor N-butyldeoxynojirimycin inhibits human immunodeficiency virus entry at the level of post-CD4 binding.
The alpha-glucosidase inhibitor N-butyldeoxynojirimycin (NB-DNJ) is a potent inhibitor of human immunodeficiency virus (HIV) replication and syncytium formation in vitro. However, the exact mechanism of action of NB-DNJ remains to be determined. In this study we have examined the impairment of HIV infectivity mediated by NB-DNJ. By two independent HIV entry assays [PCR-based HIV entry assay and entry of Cocal(HIV) pseudotypes], the reduction in infectivity was found to be due to an impairment of viral entry. No effect of NB-DNJ treatment was seen on the kinetics of the interaction between gp120 and CD4 (surface plasmon resonance; BIAcore) or on the binding of virus particles to H9 cells (using radiolabeled virions). We therefore conclude that a major mechanism of action of NB-DNJ as an inhibitor of HIV replication is the impairment of viral entry at the level of post-CD4 binding, due to an effect on viral envelope components.
Fischer
P B
PB
Department of Biochemistry, University of Oxford, United Kingdom.
Collin
M
M
Karlsson
G B
GB
James
W
W
Butters
T D
TD
Davis
S J
SJ
Gordon
S
S
Dwek
R A
RA
Platt
F M
FM
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000502:physiology*; D002460:Cell Line; D065089:Glycoside Hydrolase Inhibitors; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D011991:Receptors, Virus / Q000502:physiology; D013997:Time Factors; D014771:Virion / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D015704:CD4 Antigens; D065089:Glycoside Hydrolase Inhibitors; D015699:HIV Envelope Protein gp120; D011991:Receptors, Virus; D017485:1-Deoxynojirimycin; C059896:miglustat; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase