HIV-1 integrase-hydrolyzing IgM antibodies from sera of HIV-infected patients

Abstract

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.

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

“…However, iodoacetamide inhibited integrase hydrolyzing activities of all polyclonal IgG and IgM preparations from HIV/AIDS patients by 12-99% [97,98]. Proteolytic activities of three MLChs (18, 14, and 10) not inhibited by EDTA and PMSF were significantly suppressed by iodoacetamide, while there was no effect on the most of MLChs with metal-dependent and serinelike activities (for example, Figure 20C).…”

“…In addition, a high metal-dependent MBP-hydrolyzing activity for MS IgGs [86] and caseinhydrolyzing of human milk sIgAs [96] were recently revealed. It was shown that antiintegrase IgGs and IgMs of HIV-infected patients can contain abzymes hydrolyzing viral integrase of four types, resembling serine, thiol, metal-dependent, and acidic proteases, the ratio of which may be individual for every AIDS patient [97,98].…”

Natural Catalytic Antibodies in Norm and in HIV-Infected Patients

“…Natural Abz purification is one of the most complicated aspects of their study; it was discussed in detail in review (Nevinsky et al, 2000 b ). I n s t u d y A b z s f r o m t h e s e r a o f H I V -i n fected patients, electrophoretically and immunologically homogeneous AIDS Ab fraction (pIgG+pIgM+pIgA) was first purified by chromatography of the serum proteins on Protein A-Sepharose under conditions that remove non-specifically bound proteins Baranova et al, 2009Baranova et al, , 2010. pIgMs were separated from pIgAs and pIgGs by FPLC gel filtration of the total Ab fraction on a Superdex 200 (Baranova et al, 2009(Baranova et al, , 2010.…”

“…I n s t u d y A b z s f r o m t h e s e r a o f H I V -i n fected patients, electrophoretically and immunologically homogeneous AIDS Ab fraction (pIgG+pIgM+pIgA) was first purified by chromatography of the serum proteins on Protein A-Sepharose under conditions that remove non-specifically bound proteins Baranova et al, 2009Baranova et al, , 2010. pIgMs were separated from pIgAs and pIgGs by FPLC gel filtration of the total Ab fraction on a Superdex 200 (Baranova et al, 2009(Baranova et al, , 2010. The homogeneity of the 150 kDa IgG was confirmed by SDS-PAGE with silver staining, which showed a single band under nonreducing conditions and two bands corresponding to the H and L chains after reduction (Fig.…”

“…al., 2006 b ), and HIV-1 IN (Baranova et. al., 2009(Baranova et. al., , 2010) but not many other tested proteins.…”