HIV-1 integrase-hydrolyzing IgM antibodies from sera of HIV-infected patients.
IgG abzymes (Abzs) with different catalytic activities are a distinctive feature of various autoimmune (AI) diseases. At the same time, data concerning IgMs with catalytic activities are very limited. Electrophoretically and immunologically homogeneous IgMs were isolated from the sera of acquired immunodeficiency syndrome (AIDS) patients by chromatography on several affinity sorbents. Several rigid criteria have been applied to show that the integrase (IN)-hydrolyzing activity is an intrinsic property of IgMs from HIV-infected patients but not from healthy donors. We present evidence showing that 22 of 24 (91.7%) IgMs purified from the sera of HIV-infected patients specifically hydrolyze only HIV IN but not many other tested proteins. Usually, proteolytic antibodies of AI patients are serine protease-like or metal dependent. Only 30% of IN-hydrolyzing IgMs were inhibited by specific inhibitors of serine proteases and 60% by inhibitors of metal-dependent proteases. Unusually, a significant reduction of the activity by specific inhibitors of acidic (in 20% of IgM preparations) and thiol proteases (in 100% of IgM preparations) was observed. Although HIV infection leads to formation of antibodies to many viral and human antigens, possible biological roles for most of them are unknown. Since anti-IN IgG can efficiently hydrolyze IN, a positive role of Abzs in counteracting the infection cannot be excluded. In addition, detection of IN-hydrolyzing activity can be useful for diagnostic purposes and for assessment of the immune status in AIDS patients.
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Novosibirsk 630090, Russia.
Svetlana V
SV
Baranova
Valentina N
VN
Buneva
Marina A
MA
Kharitonova
Ludmila P
LP
Sizyakina
Christina
C
Calmels
Marie-Line
ML
Andreola
Vincent
V
Parissi
Olga D
OD
Zakharova
Georgy A
GA
Nevinsky
D000915:Antibody Affinity; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D015658:HIV Infections / Q000276:immunology*; D019427:HIV Integrase / Q000737:chemistry; D015497:HIV-1; D006801:Humans; D006868:Hydrolysis; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D013379:Substrate Specificity
D007075:Immunoglobulin M; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1