Abstract

DING proteins constitute an interesting family, owing to their intriguing and important activities. However, after a decade of research, little is known about these proteins. In humans, at least five different DING proteins have been identified, which were implicated in important biological processes and diseases, including HIV. Indeed, recent data from different research groups have highlighted the anti-HIV activity of some DING representatives. These proteins share the ability to inhibit the transcriptional step of HIV-1, a key step of the viral cycle that is not yet targeted by the current therapies. Since such proteins have been isolated from humans, we undertook a comprehensive study that focuses on the relationship between these proteins and HIV-infection in an infectious context. Hence, we developed a home-made ELISA for the quantification of the concentration of DING proteins in human serum. Using this method, we were able to determine the concentration of DING proteins in healthy and HIV-infected patients. Interestingly, we observed a significant increase of the concentration of DING proteins in non treated and treated HIV-infected patients compared to controls. In addition, cell cultures infected with HIV also show an increased expression of DING proteins, ruling out the possible role of antiretroviral treatment in the increase of the expression of DING proteins. In conclusion, results from this study show that the organism reacts to HIV-infection by an overexpression of DING proteins.

Highlights

  • DING proteins constitute an intriguing family of proteins that were named for their highly conserved N-terminal sequence DINGGG- [1,2]

  • A significant direct relationship was observed between serum DING proteins and PON1 concentrations in HIV-infected patients (r = 0.465; p,0.001; Fig. 2A), and an inverse relationship between DING proteins and PON1 lactonase (r = 20.255; p,0.001; Fig. 2B) and paraoxonase activities (r = 20.189; p = 0.008; Fig. 2C)

  • DING proteins concentration was inversely associated with serum cholesterol (r = 20.406; p,0.001; Fig. 2D), LDL-cholesterol (r = 20.310; p,0.001), high-density lipoprotein (HDL)-cholesterol (r = 20.174; p = 0.016), serum triglycerides (r = 20.146; p = 0.050), and apolipoprotein A-I (r = 20.221; p = 0.002) concentrations

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Summary

Introduction

DING proteins constitute an intriguing family of proteins that were named for their highly conserved N-terminal sequence DINGGG- [1,2]. Despite the wide presence of these proteins, DING genes have never been identified in eukaryotes, even in the human genome [5]. Attempts to sequence eukaryotic DING genes have encountered many difficulties since no ORF or locus coding these proteins has been identified. Because of the lack of available genetic information, eukaryotic DING proteins sequences are very sparse and comprise, for the most of them, only some Nterminal and internal peptides [5]. This lack of sequence information has considerably hampered studies on DING proteins, but opens a large field of investigation onto this family of proteins

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