Diversity of Integrase-Hydrolyzing IgGs and IgMs from Sera of HIV-Infected Patients

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S. V. Baranova¹, V. N. Buneva^1,2, M. A. Kharitonova³, L. P. Sizyakina³, O. D. Zakharova¹, and G. A. Nevinsky^1,2*

¹Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, pr. Lavrentieva 8, 630090 Novosibirsk, Russia; fax: (383) 363-5153; E-mail: nevinsky@niboch.nsc.ru

²Novosibirsk State University, ul. Pirogova 2, 630090 Novosibirsk, Russia

³Institute of Clinical Immunology, Rostov-on-Don State Medical University, Nakhichevansky Pereulok 29, 344022 Rostov-on-Don, Russia

^* To whom correspondence should be addressed.

Received May 26, 2011; Revision received July 15, 2011

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It was previously shown that small fractions of IgGs and IgMs from the sera of AIDS patients specifically hydrolyze only HIV integrase (IN) but not many other tested proteins. Here we present evidence showing that these IgGs and IgMs are extreme catalytically heterogeneous. Affinity chromatography on IN-Sepharose using elution of IgGs (or IgMs) with different concentration of NaCl and acidic buffer separated catalytic antibodies (ABs) into many AB subfractions demonstrating different values of K_m for IN and k_cat. Nonfractionated IgGs and IgMs possess serine-, thiol-, acidic-like, and metal-dependent proteolytic activity. Metal-dependent activity of abzymes increases in the presence of ions of different metals. In contrast to canonical proteases having one pH optimum, initial nonfractionated IgGs and IgMs demonstrate several optima at pH from 3 to 10. The data obtained show that IN-hydrolyzing polyclonal IgG and IgM of HIV-infected patients are cocktails of anti-IN ABs with different structure of the active centers possessing various affinity to IN, pH optima, and relative rates of the specific substrate hydrolysis.

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KEY WORDS: human immunodeficiency virus, abzymes, HIV infection, HIV-integrase

DOI: 10.1134/S0006297911120030

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