TY - JOUR

T1 - Hiv-infected patients: Cross site-specific hydrolysis of h3 and h4 histones and myelin basic protein with antibodies against these three proteins

AU - Baranova, Svetlana V.

AU - Dmitrenok, Pavel S.

AU - Buneva, Valentina N.

AU - Sedykh, Sergey E.

AU - Nevinsky, Georgy A.

N1 - Funding Information: This research was mostly granted from the Russian Foundation of Basic Research (20-34-70115) and (18-04-00442 A; obtaining a part of MALDI spectra). Funding Information: Sera samples of 32 patients (18–40 yr. old; women and men) were used. In accordance with the classification of the Center for Disease Control and Prevention, 19 patients correspond to the stage of generalized lymphadenopathy (GL) and 13 humans to the stage of pre-AIDS. The blood sampling protocol was supported by Novosibirsk State Medical University Ethics Committee (number 105-HIV; 07. 2010). This Standing commission endorsed this study according to Helsinki ethics committee guidelines (permission number 72-H). All patients gave written agreement to use blood samples for scientific purposes. Publisher Copyright: © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.

PY - 2021/1/2

Y1 - 2021/1/2

N2 - Histones play important roles in chromatin functioning and gene transcription, but in the intercellular space, they are harmful since they stimulate systemic inflammatory and toxic responses. Electrophoretically homogeneous IgGs against myelin basic protein (MBP), as well as H3 and H4 histones, were isolated from sera of HIV-infected patients. In contrast to known classical proteases, these IgGs split exclusively only histones and MBP but no other control proteins. Among 13 sites of hydrolysis of H3 by IgGs against H3 and 14 sites for anti-MBP IgGs, only two sites of the hydrolysis were the same. Between seven cleavage sites of H4 with IgGs against H4 and 9 sites of this histone hydrolysis by antibodies against MBP, only three sites were the same. The sites of hydrolysis of H3 (and H4) with abzymes against these histones and against MBP were different, but several expended protein clusters containing hydrolysis sites are partially overlapped. The existence of enzymatic cross-reactivity of abzymes against H3 and H4 and MBP represents a great menace to humans since due to cell apoptosis, histones constantly occur in human blood. They can hydrolyze MBP of the myelin sheath of axons and play a negative role in the pathogenesis of HIV-infected patients.

AB - Histones play important roles in chromatin functioning and gene transcription, but in the intercellular space, they are harmful since they stimulate systemic inflammatory and toxic responses. Electrophoretically homogeneous IgGs against myelin basic protein (MBP), as well as H3 and H4 histones, were isolated from sera of HIV-infected patients. In contrast to known classical proteases, these IgGs split exclusively only histones and MBP but no other control proteins. Among 13 sites of hydrolysis of H3 by IgGs against H3 and 14 sites for anti-MBP IgGs, only two sites of the hydrolysis were the same. Between seven cleavage sites of H4 with IgGs against H4 and 9 sites of this histone hydrolysis by antibodies against MBP, only three sites were the same. The sites of hydrolysis of H3 (and H4) with abzymes against these histones and against MBP were different, but several expended protein clusters containing hydrolysis sites are partially overlapped. The existence of enzymatic cross-reactivity of abzymes against H3 and H4 and MBP represents a great menace to humans since due to cell apoptosis, histones constantly occur in human blood. They can hydrolyze MBP of the myelin sheath of axons and play a negative role in the pathogenesis of HIV-infected patients.

KW - And myelin basic protein

KW - Catalytic antibodies

KW - Cross-complexation and catalytic cross-reactivity

KW - H4 histones

KW - HIV infected patients

KW - Human blood antibodies

KW - Hydrolysis of H3

KW - Humans

KW - Male

KW - HIV Infections/immunology

KW - Antigen-Antibody Reactions

KW - Hydrolysis

KW - Young Adult

KW - Histones/immunology

KW - Myelin Basic Protein/immunology

KW - Immunoglobulin G/immunology

KW - Adult

KW - Female

UR - http://www.scopus.com/inward/record.url?scp=85099888767&partnerID=8YFLogxK

U2 - 10.3390/molecules26020316

DO - 10.3390/molecules26020316

M3 - Article

C2 - 33435385

AN - SCOPUS:85099888767

VL - 26

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 2

M1 - 316

ER -