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 … Show more
“…It should be noted, however, that the association between HIV diversity and treatment outcome in this study was most striking for the pol region. While antibodies that target products of the HIV pol gene have been described [30]–[32], those proteins are not primary targets of the humoral immune response to HIV infection.…”
BackgroundIn HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6–36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth.MethodsHIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions).ResultsIn multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P<0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures).ConclusionsIn this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.
“…It should be noted, however, that the association between HIV diversity and treatment outcome in this study was most striking for the pol region. While antibodies that target products of the HIV pol gene have been described [30]–[32], those proteins are not primary targets of the humoral immune response to HIV infection.…”
BackgroundIn HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6–36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth.MethodsHIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions).ResultsIn multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P<0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures).ConclusionsIn this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.
“…It should be noted, however, that the association between HIV diversity and treatment outcome in this study was most striking for the pol region. While antibodies that target products of the HIV pol gene have been described [30][31][32], those proteins are not primary targets of the humoral immune response to HIV infection. Alternatively, higher levels of pol diversity prior to ART initiation may reflect properties of the viral strain, such as faster replication.…”
Background:In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6-36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth.Methods: HIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions).
Results:In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P,0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pretreatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P,0.001 for all measures).
Conclusions:In this cohort of sdNVP-exposed, ART-naı ¨ve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.
“…Metal-dependent IgGs and/or IgMs from the blood of HIV-infected patients hydrolyzing DNA [69], viral reverse transcriptase [102] and integrase [103][104][105], and all histones [106] were described. Average activities of anti-IN IgGs in the hydrolysis of IN decreased in the order Mn 2+ > Mg 2+ ≈ Cu 2+ > Co 2+ while for IgMs in another order Cu 2+ > Mn 2+ > Co 2+ ≫ Mg 2+ .…”
Section: Catalytic Activities Of Antibodies Of Hiv-infected Patientsmentioning
Microelements play different important roles in many physiological processes in all biological systems in both normal physiological and pathological conditions. They take part in the transport of nutrients and gases, support temperature, acid-base balance, homeostasis of the human organisms, maternal and child mental health, the functioning of enzymes, protein and DNA syntheses, cytoskeleton activation, etc. We have performed simultaneous determination of a number of minor and trace elements in whole blood and tissues of mammals by two-jet plasma atomic emission spectrometry (TJP-AES). TJP-AES allows direct analysis of powders without wet acid digestion and can be used for analysis of both large and small amount of the sample, which is important for biomedical investigations with humans and experimental animals. In addition, a content of different elements in preparations of human immunoglobulins was estimated by TJP-AES as well as using different physicochemical methods, the functional role of metal ions in antibodies functioning was analyzed. The analysis of the relative activity of antibodies with catalytic activity (abzymes) in the hydrolysis of DNA, RNA, proteins, peptides and oxidation-reduction reactions and the role of metal ions in the catalysis of these reactions by abzymes were carried out.
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