Regulatory role of phospholipids in hepatitis C virus replication and protein function

  • Positive-strand RNA viruses such as hepatitis C virus (HCV) hijack key factors of lipid metabolism of infected cells and extensively modify intracellular membranes to support the viral lifecycle. While lipid metabolism plays key roles in viral particle assembly and maturation, viral RNA synthesis is closely linked to the remodeling of intracellular membranes. The formation of viral replication factories requires a number of interactions between virus proteins and host factors including lipids. The structure–function relationship of those proteins is influenced by their lipid environments and lipids that selectively modulate protein function. Here, we review our current understanding on the roles of phospholipids in HCV replication and of lipid–protein interactions in the structure–function relationship of the NS5A protein. NS5A is a key factor in membrane remodeling in HCV-infected cells and is known to recruit phosphatidylinositol 4-kinase III alpha to generate phosphatidylinositol 4-phosphate at the sites of replication. The dynamic interplay between lipids and viral proteins within intracellular membranes is likely key towards understanding basic mechanisms in the pathobiology of virus diseases, the mode of action of specific antiviral agents and related drug resistance mechanisms.

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Author:Anna Valentinovna BulankinaGND, Rebecca M. RichterORCiD, Christoph WelschORCiDGND
Parent Title (English):Pathogens
Place of publication:Basel
Document Type:Article
Date of Publication (online):2022/01/15
Date of first Publication:2022/01/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/11/16
Tag:NS5A; RNA virus; hepatitis C virus; interactions; membrane remodeling; phospholipid; viral replication
Issue:1, art. 102
Article Number:102
Page Number:15
First Page:1
Last Page:15
This research was funded by the German Research Foundation grant entitled “Role of the lipid environment in NS5A structural rearrangements and drug interactions in hepatitis C” (WE 4388/8-1), the Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) of the State of Hessen, Research Center for Translational Medicine and Pharmacology TMP, the Else Kröner-Fresenius-Foundation (EKFS), Research Training Group Translational Research Innovation-Pharma (TRIP), and the Gilead Sciences International Research Scholars Program in Liver Disease.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International