Abstract
BackgroundThe pathophysiological overlapping between Sjorgen’s Syndrome (SS) and HCV, presence of anti- muscarinic receptor type 3 (M3R) antibodies in SS, the role that M3R plays in the regulation of the heart rate, has led to the assumption that cardiovagal dysfunction in HCV patients is caused by anti-M3R antibodies elicited by HCV proteins or by their direct interaction with M3R.ResultsTo identify HCV protein which possibly is crossreactive with M3R or which binds to this receptor, we performed the Informational Spectrum Method (ISM) analysis of the HCV proteome. This analysis revealed that NS5A protein represents the most probable interactor of M3R or that this viral protein could elicit antibodies which modulate function of this receptor. Further detailed structure/function analysis of NS5A and M3R performed by the ISM method extended with other Digital Signal processing (DSP) approaches revealed domains of these proteins which participate in their crossreactivity or in their direct interaction, representing promising diagnostic and therapeutic targets.ConclusionsApplication of the ISM with other compatible bioinformatics methods offers new perspectives for identifying diagnostic and therapeutic targets for complicated forms of HCV and other viral infections. We show how the electron-ion interaction potential (EIIP) amino-acid scale used in the ISM combined with a robust, high performance hydrophobicity scale can provide new insights for understanding protein structure/function and protein-protein interactions.
Highlights
The pathophysiological overlapping between Sjorgen’s Syndrome (SS) and hepatitis C virus (HCV), presence of antimuscarinic receptor type 3 (M3R) antibodies in SS, the role that muscarinic type 3 receptor (M3R) plays in the regulation of the heart rate, has led to the assumption that cardiovagal dysfunction in HCV patients is caused by anti-M3R antibodies elicited by HCV proteins or by their direct interaction with M3R
We show that Informational Spectrum Method (ISM) extended with other Digital Signal processing (DSP) approaches provides a unique way to understand the formation of protein domains and relation of primary sequence to the formation of secondary structure and the location of epitopes
Calculation of the cross-spectrum (CS) between M3R and each protein from the EUHCV database revealed that maximal amplitudes and signal-to-noise ratio (S/N) corresponds to the CS relationship between the M3R and HCV NS5A proteins, and that f(0.158) represents the common frequency component in informational spectra (IS) for these two proteins using the electron-ion interaction potential (EIIP) scale
Summary
The pathophysiological overlapping between Sjorgen’s Syndrome (SS) and HCV, presence of antimuscarinic receptor type 3 (M3R) antibodies in SS, the role that M3R plays in the regulation of the heart rate, has led to the assumption that cardiovagal dysfunction in HCV patients is caused by anti-M3R antibodies elicited by HCV proteins or by their direct interaction with M3R. We show that ISM extended with other Digital Signal processing (DSP) approaches provides a unique way to understand the formation of protein domains and relation of primary sequence to the formation of secondary structure and the location of epitopes. We have used this method to understand virus-induced autoimmune diseases. Lymphoproliferative disorders usually accompany persistent hepatitis C virus (HCV) infection [4]. This leads to a number of extra-hepatic manifestations [5] one of them being the Sjögren’s syndrome (SS). The association was confirmed both in the primary and secondary forms of this syndrome [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
