Τίτλος:
The unexpected function of a highly conserved YXXΦ motif in HCV core protein
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Hepatitis C virus (HCV) is an RNA positive strand virus, member of the Flaviviridae family. The HCV viral particle is composed of a capsid containing the genome, surrounded by an endoplasmic reticulum (ER)-derived lipid bilayer where E1 and E2 are assembled as heterodimers. However, different forms of viral particles have been identified in the serum of HCV-infected patients, including non-enveloped particles. Previous reports have demonstrated that HCV non-enveloped capsid-like particles (HCVne) can be generated by HCV core protein sequence. This sequence possesses a highly conserved ΥΧΧΦ motif and distal di-leucine motifs that confer primary endocytosis signals, enabling HCVne to enter hepatic cells via clathrin-mediated endocytosis. Although HCV core's primary function is to encapsidate the viral genome, it also interacts with a variety of cellular proteins in order to regulate host cell functions such as gene transcription, lipid metabolism, apoptosis and several signaling pathways. In this report, we demonstrate that the YXXΦ motif of HCV core protein is crucial for the architectural integrity of the particulate form of HCVne. Moreover, we show that the YXXΦ motif in the HCV core sequence plays a pivotal role in the signaling events following HCVne clathrin-mediated endocytosis by inducing the AP-2 clathrin adaptor protein, which in turn redirect HCVne trafficking to the lipid droplets (LDs) via the endosomal-lysosomal pathway. HCVne and LDs co-localization affects the HCV life cycle by enhancing viral replication. © 2017 Elsevier B.V.
Συγγραφείς:
Karamichali, E.
Serti, E.
Gianneli, A.
Papaefthymiou, A.
Kakkanas, A.
Foka, P.
Seremetakis, A.
Katsarou, K.
Trougakos, I.P.
Georgopoulou, U.
Περιοδικό:
Infection, Genetics and Evolution
Λέξεις-κλειδιά:
adaptor protein; cell protein; clathrin; core protein; fat droplet; leucine; protein YXXphi; unclassified drug; core protein; nucleocapsid protein, Hepatitis C virus, apoptosis; Article; conserved sequence; endocytosis; endosome; genetic transcription; Hepatitis C virus; host cell; human; human cell; life cycle; lipid metabolism; liver cell; lysosome; nonhuman; priority journal; protein function; protein localization; protein motif; protein protein interaction; protein structure; regulatory mechanism; signal transduction; virus genome; virus replication; amino acid sequence; cell culture; cell line; chemistry; genetic recombination; genetics; Hepacivirus; hepatitis C; mutation; protein motif; ultrastructure; virology, Amino Acid Motifs; Amino Acid Sequence; Cell Line; Cells, Cultured; Conserved Sequence; Hepacivirus; Hepatitis C; Humans; Mutation; Recombination, Genetic; Viral Core Proteins; Virus Replication
DOI:
10.1016/j.meegid.2017.07.001
