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Diversity of integrase-hydrolyzing IgGs and IgMs from sera of HIV-infected patients

Biochemistry (Moscow) volume 76, pages 1300–1311 (2011)Cite this article

Abstract

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-, acidiclike, 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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Abbreviations

AB:

antibodies

ABappl, ABNaCl, and ABacid :

fractions of antibodies eluted from IN-Sepharose on application, with NaCl gradient concentration, and with acidic buffer, respectively

AIDS:

acquired immunodeficiency syndrome

HIV:

human immunodeficiency virus

IN:

HIV-integrase

HSA:

human serum albumin

MBP:

myelin basic protein

pIgG, pIgM, and pIgA:

polyclonal IgG, IgM, and IgA

SLE:

systemic lupus erythematosus

VIP:

vasoactive intestinal peptide

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Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, pr. Lavrentieva 8, 630090, Novosibirsk, Russia

    S. V. Baranova, V. N. Buneva, O. D. Zakharova & G. A. Nevinsky

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

    V. N. Buneva & G. A. Nevinsky

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

    M. A. Kharitonova & L. P. Sizyakina

Authors
  1. S. V. Baranova
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  2. V. N. Buneva
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  3. M. A. Kharitonova
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  4. L. P. Sizyakina
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  5. O. D. Zakharova
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  6. G. A. Nevinsky
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Corresponding author

Correspondence to G. A. Nevinsky.

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Original Russian Text © S. V. Baranova, V. N. Buneva, M. A. Kharitonova, L. P. Sizyakina, O. D. Zakharova, G. A. Nevinsky, 2011, published in Biokhimiya, 2011, Vol. 76, No. 12, pp. 1615–1628.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM11-164, October 9, 2011.

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Baranova, S.V., Buneva, V.N., Kharitonova, M.A. et al. Diversity of integrase-hydrolyzing IgGs and IgMs from sera of HIV-infected patients. Biochemistry Moscow 76, 1300–1311 (2011). https://doi.org/10.1134/S0006297911120030

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  • DOI: https://doi.org/10.1134/S0006297911120030

Key words

  • human immunodeficiency virus
  • abzymes
  • HIV infection
  • HIV-integrase