Phosphorylated tyrosine 93 of hepatitis C virus nonstructural protein 5A is essential for interaction with host c-Src and efficient viral replication.

The hepatitis C virus (HCV) nonstructural protein 5A (NS5A) plays a key role in viral replication and virion assembly, and the regulation of the assembly process critically depends on phosphorylation of both serine and threonine residues in NS5A. We previously identified SRC proto-oncogene, nonreceptor tyrosine kinase (c-Src), as an essential host component of the HCV replication complex consisting of NS5A, the RNA-dependent RNA polymerase NS5B, and c-Src. Pulldown assays revealed an interaction between NS5A and the Src homology 2 (SH2) domain of c-Src; however, the precise binding mode remains undefined.

HCV modifies EGF signalling and upregulates production of CXCR2 ligands: Role in inflammation and antiviral immune response.

Background & Aims: To affect immune response and inflammation, the hepatitis C virus (HCV) substantially influences intercellular communication pathways that are decisive for immune cell recruitment. The present study investigates mechanisms by which HCV modulates chemokine-mediated intercellular communication from infected cells.

Methods: Chemokine expression was studied in HCV-infected cell lines or cell lines harbouring a subgenomic replicon, as well as in serum samples from patients.

Hepatitis C Virus Activates a Neuregulin-Driven Circuit to Modify Surface Expression of Growth Factor Receptors of the ErbB Family.

Recently, the epidermal growth factor (EGF) receptor (EGFR), a member of the ErbB receptor family, and its down-stream signalling have been identified as co-factors for HCV entry and replication. Since EGFR also functions as a heterodimer with other ErbB receptor family members, the subject of the present study was to investigate a possible viral interference with these cellular components. By using genotype 1b replicon cells as well as an infection-based system we found that while transcript and protein levels of EGFR and ErbB2 were up-regulated or unaffected, respectively, HCV induced a substantial reduction of ErbB3 and ErbB4 expression.