Catalytic antibodies from HIV-infected patients specifically hydrolyzing viral integrase suppress the enzyme catalytic activities.
Human immunodeficiency virus type 1 integrase (IN) catalyzes integration of a DNA copy of the viral genome into the host genome. It was shown previously that IN preincubation with various oligodeoxynucleotides (ODNs) induces formation of dimers and oligomers of different gyration radii; only specific ODNs stimulate the formation of catalytically active dimers. Here we have shown that preincubation of IN with specific and nonspecific ODNs leads to a significant and comparable decrease in its hydrolysis by chymotrypsin, while nonspecific ODNs protect the enzyme from the hydrolysis by trypsin worse than specific ODNs; all ODNs had little effect on the IN hydrolysis by proteinase K. In contrast to canonical proteweases, IgGs from HIV-infected patients specifically hydrolyze only IN. While d(pT)(n) markedly decreased the IgG-dependent hydrolysis of IN, d(pA)(n) and d(pA)(n) •d(pT)(n) demonstrated no detectable protective effect. The best protection from the hydrolysis by IgGs was observed for specific single- and especially double-stranded ODNs. Although IN was considerably protected by specific ODNs, proteolytic IgGs and IgMs significantly suppressed both 3'-processing and integration reaction catalyzed by IN. Since anti-IN IgGs and IgMs can efficiently hydrolyze IN, a positive role of abzymes in counteracting the infection cannot be excluded.
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 8 Lavrentiev Ave., Novosibirsk, 630090, Russia.
Elena S
ES
Odintsova
Svetlana V
SV
Baranova
Valentina N
VN
Buneva
Christina
C
Calmels
Vincent
V
Parissi
Marie-Line
ML
Andreola
Olga D
OD
Zakharova
Georgy A
GA
Nevinsky
D000293:Adolescent; D000328:Adult; D017151:Antibodies, Catalytic / Q000737:chemistry*; D002384:Catalysis; D002918:Chymotrypsin / Q000737:chemistry; D019281:Dimerization; D019286:Endopeptidase K / Q000737:chemistry; D005260:Female; D015483:HIV Antibodies / Q000737:chemistry*; D015658:HIV Infections / Q000276:immunology*; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000737:chemistry*; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
D017151:Antibodies, Catalytic; D015483:HIV Antibodies; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D019427:HIV Integrase; D002918:Chymotrypsin; D019286:Endopeptidase K