Antibody-independent, complement-mediated enhancement of HIV-1 infection by mannosidase I and II inhibitors.
Human immunodeficiency virus type 1 (HIV-1) infectivity and cytopathic effect require proper maturation of the viral envelope glycoprotein carbohydrate moieties. We have found that fresh human serum enhances the infectivity of HIV-1 in MT-2 cell infection assays when virus is synthesized in the presence of the mannosidase I inhibitor, 1-deoxymannojirimycin, or the mannosidase II inhibitor, swainsonine, but has no enhancing effect on virus synthesized in the presence of the glucosidase I inhibitors, castanospermine and 1-deoxynojirimycin, or the glucosidase II inhibitor, bromoconduritol. Enhanced infections were characterized by cytopathic effect, antigen synthesis and reverse transcriptase release, all which occurred sooner than in control-infected cultures. This enhancement of infection was also observed in C1q-deficient serum but was not observed in serum that was heat-inactivated or depleted of complement components C3 or factor B, thus suggesting a requirement for the alternate pathway of complement.
Montefiori
D C
DC
Department of Pathology, Vanderbilt University, School of Medicine, Nashville, TN 37232.
Robinson
W E
WE
Mitchell
W M
WM
D017485:1-Deoxynojirimycin; D000470:Alkaloids / Q000494:pharmacology*; D002478:Cells, Cultured; D003176:Complement C3 / Q000276:immunology; D011415:Complement Factor B / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors; D006031:Glycosylation; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D017026:Swainsonine
D000470:Alkaloids; D003176:Complement C3; D017485:1-Deoxynojirimycin; D003165:Complement System Proteins; D012194:RNA-Directed DNA Polymerase; D005959:Glucosidases; D008361:Mannosidases; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase; C038829:mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase; D011415:Complement Factor B; D005944:Glucosamine; D017026:Swainsonine