Abstract
BackgroundPlasma proteins are known to interfere the drug metabolism during therapy. As limited information is available regarding the role of plasma proteins in HIV drug resistance during ART in HIV/AIDS patients, the present study aimed to identify and characterize the differentially expressed plasma proteins in the drug resistant and drug respondent groups of HIV-1 infected patients with > 6 years of first line ART.MethodsFour-drug resistant (treatment failure) and four-drug respondent (treatment responder) patients were selected for plasma proteomic analysis based on viral load and drug resistance associated mutations from a cohort study designed on the first line ART patients who were enrolled in the antiretroviral therapy center, Sarojini Naidu Medical College, Agra, India from December 2009 to November 2016.After depleting high abundant proteins, plasma proteins were resolved using two-dimensional gel electrophoresis on IPG strips, pH range of 3–10. Spots were selected in the gel based on the density of staining which was common in the drug resistant and drug respondent groups separately. The fold change of each spot was calculated using image-J. Each protein spot was identified using the matrix assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) after tryptic digestion. Peptide peaks were identified through flex analysis version 3.3, and a search against a protein data base using the internal Mascot. Gene ontology study was completed through STRING v.11 and Panther15.0.ResultsOut of eight spots from 2D gel samples analyzed by MALDITOF/TOF, two proteins were found to have significant score (> 56) after Flex analysis. These two proteins were identified to be apolipoprotein A1 and serotransferrin. The fold change expression of these two proteins were analyzed in drug resistant and drug respondent group. Apolipoprotein-A1 and serotransferrin were observed to be expressed 1.76 and 1.13-fold more respectively in drug respondent group compared to drug resistant group. The gene ontology analysis revealed the involvement of these two proteins in various important physiological processes.ConclusionApolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group.
Highlights
Plasma proteins are known to interfere the drug metabolism during therapy
Apolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group
The drug resistant group considered as treatment failure and drug respondent group had no nucleoside reverse transcriptase inhibitors (NRTIs) and nucleoside reverse transcriptase inhibitors (NNRTIs) associated mutations in the reverse transcriptase gene of Human immunodeficiency virus (HIV)-1
Summary
Plasma proteins are known to interfere the drug metabolism during therapy. There has been concern that changes in protein binding could impact on antiviral activity and management. Changes in protein binding could impact antiviral activity in the host [5]. Plasma protein binding to the drugs and its effective modulation in drug metabolism help in drug discovery and development of new drug therapy [6]. Human saliva or serum proteins were identified through MALDI-TOF/ MS for biomarker discovery [8, 9]. The gene or protein diversity study aid in discovery of clinical biomarker. We attempted to identify the plasma proteins in drug resistant (treatment failure) and drug respondent (treatment responder) groups of HIV-1 patients who were treated with first-line ART over 6 years
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