TY  - JOUR
A1  - Bulankina, Anna Valentinovna
A1  - Richter, Rebecca M.
A1  - Welsch, Christoph
T1  - Regulatory role of phospholipids in hepatitis C virus replication and protein function
T2  - Pathogens
N2  - 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.
KW  - RNA virus
KW  - hepatitis C virus
KW  - phospholipid
KW  - viral replication
KW  - membrane remodeling
KW  - interactions
KW  - NS5A
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/79548
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-795483
SN  - 2076-0817
N1  - 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.
VL  - 11
IS  - 1, art.  102
SP  - 1
EP  - 15
PB  - MDPI
CY  - Basel
ER  -