Alkaloidal glycosidase inhibitors (AGIs) as the cause of sporadic scrapie, and the potential treatment of both transmissible spongiform encephalopathies (TSEs) and human immunodeficiency virus (HIV) infection.
AGIs are produced by plants and microorgansims in the environment. They are absorbed from the gut, distributed throughout the body and are concentrated inside cells. AGIs alter the glycan chains of cellular glycoproteins (CGP) during their formation so that the same CGP produced by different clones of cells (and hence with different glycan chains) becomes structurally the same. Prion protein (PrP), a CGP, is rendered indestructable to cellular mechanisms (as PrPi) by the TSE infective process; it is suggested that AGIs could both cause and prevent this by altering the primary structure of PrP. HIV envelope protein, gp120, carries glycan chains that are decided by the clone of the cells by which it is produced. Each cellular clone would be expected to add a specific group of glycan chains, making the gp120 antigenically separate. As HIV infection progresses, infected clone numbers rise, the antigenic diversity of gp120 may rise as would antibody production, trying to keep pace. Antigenically stimulated CD4+ cells carrying HIV genes, increase HIV production with gp120 antigenically different from its stimulant. AGIs prevent the glycan diversity and may prevent the extension of HIV infection.
Dealler
S
S
York District Hospital Microbiology Department, UK.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000940:Antigenic Variation / Q000187:drug effects; D007562:Creutzfeldt-Jakob Syndrome / Q000209:etiology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008954:Models, Biological; D017096:Prion Diseases / Q000188:drug therapy; D011328:Prions / Q000737:chemistry / Q000378:metabolism; D012608:Scrapie / Q000209:etiology*
D000470:Alkaloids; D015699:HIV Envelope Protein gp120; D011328:Prions; D006026:Glycoside Hydrolases