Establishment of a miRNA profile in paediatric HIV-1 patients and its potential as a biomarker for effectiveness of the combined antiretroviral therapy

AbstractmiRNAs have been extensively studied in pathological conditions, including viral infections, such as those provoked by HIV-1. Several cellular and circulating miRNAs are altered during HIV-1 infection, with either beneficial effects on host defenses or enhanced virus infectivity. Blood samples were collected in sterile EDTA tubes and plasma was separated and stored, as were PBMCs. RNA was isolated and reverse-transcribed. Finally, the miRNA gene expression profile was assessed using TaqMan Array Human microRNA Card A v2.0. A comprehensive statistical analysis was performed on the results obtained. This is the first study on miRNAs in HIV-1 paediatric patients, and a miRNA profile differentiating patients starting combination antiretroviral therapy (cART) at different times after HIV-1 diagnosis was established. Thirty-four miRNAs were observed to have different expression levels between the control group and the cART group. The data indicates the need to start cART as soon as possible after the establishment of HIV-1 infection to assure the best outcome possible. Finally, the selected 34 miRNAs may be used as biomarkers for prognosis and assessing therapy effectiveness. However, more research must be conducted to establish adequate quantitative correlations.

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Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives

Advances in Biology ◽

10.1155/2014/157895 ◽

2014 ◽

Vol 2014 ◽

pp. 1-24 ◽

Cited By ~ 71

Author(s):

P. J. Klasse

Keyword(s):

Cellular Immunity ◽

Neutralizing Antibodies ◽

Viral Infections ◽

Viral Proteins ◽

Virus Neutralization ◽

Virus Infectivity ◽

Viral Pathogens ◽

Enveloped Viruses ◽

Vaccine Candidates ◽

Hiv 1

Neutralizing antibodies (NAbs) can be both sufficient and necessary for protection against viral infections, although they sometimes act in concert with cellular immunity. Successful vaccines against viruses induce NAbs but vaccine candidates against some major viral pathogens, including HIV-1, have failed to induce potent and effective such responses. Theories of how antibodies neutralize virus infectivity have been formulated and experimentally tested since the 1930s; and controversies about the mechanistic and quantitative bases for neutralization have continually arisen. Soluble versions of native oligomeric viral proteins that mimic the functional targets of neutralizing antibodies now allow the measurement of the relevant affinities of NAbs. Thereby the neutralizing occupancies on virions can be estimated and related to the potency of the NAbs. Furthermore, the kinetics and stoichiometry of NAb binding can be compared with neutralizing efficacy. Recently, the fundamental discovery that the intracellular factor TRIM21 determines the degree of neutralization of adenovirus has provided new mechanistic and quantitative insights. Since TRIM21 resides in the cytoplasm, it would not affect the neutralization of enveloped viruses, but its range of activity against naked viruses will be important to uncover. These developments bring together the old problems of virus neutralization—mechanism, stoichiometry, kinetics, and efficacy—from surprising new angles.

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Low Complication Rate Associated with Cesarean Section under Spinal Anesthesia for HIV-1–Infected Women on Antiretroviral Therapy

Anesthesiology ◽

10.1097/00000542-200208000-00006 ◽

2002 ◽

Vol 97 (2) ◽

pp. 320-324 ◽

Cited By ~ 44

Author(s):

Michael S. Avidan ◽

Philippa Groves ◽

Margaret Blott ◽

Jan Welch ◽

Theresa Leung ◽

...

Keyword(s):

Viral Load ◽

Antiretroviral Therapy ◽

Postoperative Complications ◽

Cesarean Section ◽

Spinal Anesthesia ◽

Elective Cesarean Section ◽

Controlled Study ◽

Control Group ◽

Elective Cesarean ◽

Hiv 1

Background Elective cesarean section decreases the likelihood of vertical human immunodeficiency virus (HIV) transmission from mother to infant. This study aimed to determine whether cesarean section done with spinal anesthesia on HIV-1-infected pregnant women taking antiretroviral therapy is associated with intraoperative hemodynamic instability, postoperative complications, or changes in immune function or HIV-1 viral load. Methods A case-controlled study was conducted over a 3-year period in a London academic hospital. Forty-four women infected with HIV-1 and a control group of 45 HIV-negative women undergoing cesarean sections were included. The main outcome measures included intraoperative blood pressure, heart rate, blood loss, and ephedrine requirements, and postoperative infective complications, blood transfusion, changes in blood HIV-1 viral load and lymphocyte subsets, and time to hospital discharge. Results There were no differences in hemodynamic stability and postoperative complications between the HIV-infected group and the controls. There was an acute postoperative increase in the CD4T lymphocyte count (P = 0.01), but the CD4T:CD8T ratio and viral load did not change. Conclusions Elective cesarean section under spinal anesthesia for women infected with HIV-1 taking antiretroviral therapy was not associated with intraoperative or postoperative complications.

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Blood Cell Membrane Fluidity and Intracellular Ca2+Changes in Antiretroviral-Naïve and -Treated HIV-1–Infected Patients

The Scientific World JOURNAL ◽

10.1100/tsw.2010.34 ◽

2010 ◽

Vol 10 ◽

pp. 350-355

Author(s):

Nuno C. Santos ◽

J. Martins e Silva ◽

Teresa Freitas ◽

M. Doroana ◽

N. Duarte ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Membrane Fluidity ◽

Highly Active Antiretroviral Therapy ◽

Calcium Concentration ◽

Infectious Virus ◽

Control Group ◽

Cell Infection ◽

Highly Active ◽

Cell Membrane Fluidity ◽

Hiv 1

We previously showed that lymphocytes and erythrocytes of HIV-1–infected patients, prior to antiretroviral therapy, presented significant changes in intracellular calcium concentration ([Ca2+]int) and membrane fluidity. The present study evaluates the same parameters after response to highly active antiretroviral therapy (HAART). Blood samples were collected from patients prior to and after antiretroviral therapy, and from control subjects. Membrane fluidity and [Ca2+]intwere assessed by fluorescence spectroscopy measurements, using three different probes: TMA-DPH and DPH for membrane fluidity, and fura-2 for Ca2+. When compared with the control group, both untreated and treated patients presented increased lymphocyte [Ca2+]intand decreased lymphocyte membrane fluidity, without significant differences between the two groups of patients. On the contrary, the therapy reversed the membrane fluidity variations observed in erythrocytes. The decreased erythrocyte [Ca2+]intof untreated patients was not reversed by HAART. AIDS patients present changes in lymphocyte (mostly noninfected) and erythrocyte properties, partially reversed by HAART, consistent with a process of facilitated propagation of the infection to new cells, stimulation of virion production, and maintenance of a reservoir of erythrocyte-bound infectious virus. These observations can be related with the action of the HIV Nef protein in the cell's proteins and lipid composition, as well as with the recently observed cell infection by HIV-1 via endocytosis.

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