HIV-1 integrase-hydrolyzing antibodies from sera of HIV-infected patients.
Autoantibodies with enzymic activities (abzymes) are a distinctive feature of autoimmune diseases. It was interesting whether Abs from patients with viral diseases can hydrolyze viral proteins. Electrophoretically and immunologically homogeneous IgGs were isolated from sera of AIDS patients by chromatography on several affinity sorbents. We present evidence showing that 89.5% IgGs purified from the sera of HIV-infected patients using several affinity resins including Sepharose with immobilized integrase specifically hydrolyze only HIV integrase (IN) but not many other tested proteins. Several rigid criteria have been applied to show that the IN-hydrolyzing activity is an intrinsic property of AIDS IgGs but not from healthy donors. Similar to autoimmune proteolytic abzymes, IN-hydrolyzing IgGs from some patients were inhibited by specific inhibitors of serine and metal-dependent proteases but a significant inhibition of the activity by specific inhibitors of acidic- and thiol-like proteases was observed for the first time. Although HIV infection leads to formation of Abs to many viral and human antigens, no possible biological role for most of them is known. Since anti-IN IgG can efficiently hydrolyze IN, a positive role of abzymes in counteracting the infection cannot be excluded. In addition, detection of IN-hydrolyzing activity can be useful for diagnostic purposes and for estimation of the immune status in AIDS patients.
Baranova
Svetlana V
SV
Siberian Division of Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia.
Buneva
Valentina N
VN
Kharitonova
Marina A
MA
Sizyakina
Ludmila P
LP
Calmels
Christina
C
Andreola
Marie-Line
ML
Parissi
Vincent
V
Nevinsky
Georgy A
GA
D000293:Adolescent; D000328:Adult; D017151:Antibodies, Catalytic / Q000302:isolation & purification / Q000378:metabolism*; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000201:enzymology* / Q000276:immunology*; D019427:HIV Integrase / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D010436:Pepstatins / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D055815:Young Adult
D017151:Antibodies, Catalytic; D007976:Leupeptins; D010436:Pepstatins; D011480:Protease Inhibitors; D013450:Sulfones; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D019427:HIV Integrase; C032854:leupeptin; C031375:pepstatin