Inhibition of HIV and SIV infectivity by blockade of alpha-glucosidase activity.
Processing of HIV and SIV envelope oligosaccharides is critical for proper intracellular trafficking and function. An inhibitor of alpha-glucosidases I and II, N-butyl deoxynojirimycin (N-BuDNJ), retards HIV-1 and SIVmac spread in lymphocytes and monocytes by diminishing virus infectivity, and also causes a reduction in syncytia formation between infected cells and uninfected lymphocytes. N-BuDNJ retards envelope processing from the precursor form to the mature surface (SU) and transmembrane proteins in HIV-1- and SIVmac-infected cells, as well as in cells infected with vaccinia-HIV-1 envelope recombinant virus. However, no significant reduction is seen in the amount of SU in released virus particles, though the virus particle-associated SU from N-BuDNJ-treated cells has an altered electrophoretic mobility. In contrast, N-BuDNJ had no effect on GAG protein synthesis and processing. These findings demonstrate a critical requirement for oligosaccharide processing by alpha-glucosidases I and II for HIV-1 and SIVmac envelope processing and fusogenicity.
Ratner
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L
Department of Medicine, Washington University, St. Louis, Missouri 63110.
vander Heyden
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N
Dedera
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D
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006678:HIV / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009844:Oligosaccharides / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011995:Recombination, Genetic; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics*; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D065089:Glycoside Hydrolase Inhibitors; D009844:Oligosaccharides; D014759:Viral Envelope Proteins; D017485:1-Deoxynojirimycin; C059896:miglustat; D012194:RNA-Directed DNA Polymerase; D005944:Glucosamine