Attenuation of HIV-1 infectivity by an inhibitor of oligosaccharide processing.
A series of inhibitors of trimming glucosidases and mannosidases were examined for antiviral activity toward HIV-1. N-butyl deoxynojirimycin (N-buDNJ) was found to be the most potent agent studied. Treatment of acutely infected lymphoid cells with 2.0 mM N-buDNJ reduced virus yield more than 90%, without affecting cell growth. Though lower concentrations of N-buDNJ (0.002-0.2 mM) did not affect HIV-1 production, there was complete inhibition of syncytia formation. Treatment of chronically infected lymphoid cells with 0.1-1.0 mM N-buDNJ resulted in no significant change in virus production, but 80% reduction of infectivity. The attenuation in HIV-1 infectivity was due at least partially to diminished binding to CD4+ lymphoid cells. Chronically infected lymphoid cells treated with 0.02-1.0 mM N-buDNJ for at least 3 days were markedly impaired in their ability to form syncytia with uninfected lymphoid cells. N-buDNJ treatment of HIV-1 infected cells resulted in both a reduction in the cell surface envelope proteins, and an increase in their apparent molecular weight. These results show that N-buDNJ can be used to impair the infectivity of HIV-1 without significant toxicity.
Dedera
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Department of Medicine, Washington University, St. Louis, Missouri 63110.
Vander Heyden
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N
Ratner
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L
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000606:Amino Sugars / Q000494:pharmacology; D000998:Antiviral Agents; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D009844:Oligosaccharides / Q000378:metabolism*; D014774:Virulence / Q000187:drug effects
D000606:Amino Sugars; D000998:Antiviral Agents; D009844:Oligosaccharides; D017485:1-Deoxynojirimycin; C059896:miglustat; D005959:Glucosidases; D005944:Glucosamine