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Intrinsic Disorder Angle of the HCV Co-Infection and Super-Infection with Other Hepatitis Viruses

This version is not peer-reviewed.

Submitted:

03 February 2025

Posted:

04 February 2025

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Abstract
There are five different types of the hepatotropic hepatitis viruses (HAV, HBV, HCV, HDV, and HEV). Infection with all hepatitis viruses leads to the development of disease, and all of them are capable of co-infection and super-infection; i.e., the presence of more than one type of hepatitis virus in an infected individual. Typically, co-infections cause more severe illness. Although many facets of virus-host interactions are known, important aspects related to the prevalence and functionality of intrinsic disorder in viral interactomes remain mostly unexplored. Even less is known about prevalence and roles of intrinsic disorder in proteins related to the hepatotropic co-infections. The goal of this study is to fill this gap by conducting the bioinformatics analysis of intrinsic disorder in host proteins interacting with hepatotropic viruses, with special focus on host proteins that can interact with more than one type of hepatitis viruses. To this end, a set of computational tools was used to evaluate disorder status of proteins, their predisposition for liquid-liquid phase separation (LLPS), and interactivity. This analysis revealed that some viral proteins were predicted to have high LLPS potential. Host proteins interacting with hepatotropic viruses were characterized by noticeable variation in their intrinsic disorder status and LLPS potential. Although global disorder distribution within the sets of host proteins interacting with hepatitis viruses was not too different from that of the entire human proteome, more host proteins interacting with hepatitis viruses were predicted as moderately disordered in comparison with the entire human proteome. Intrinsic disorder was shown to be commonly present in host proteins shared by several hepatotropic viruses, where it is used for various functional properties.
Keywords: 
HAV; HBV; HCV; HDV; HEV; viral co-infection; intrinsically disordered proteins; liquid-liquid phase separation; protein-protein interactions; PPI network
Subject: 
Biology and Life Sciences  -   Life Sciences
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.

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