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Hepatitis C virus up-regulates B-cell receptor signaling: a novel mechanism for HCV-associated B-cell lymphoproliferative disorders

ABSTRACT: B-cell receptor (BCR) signaling is essential for the development of B-cells and plays a critical role in B-cell neoplasia. Increasing evidence indicates an association between chronic hepatitis C virus (HCV) infection and B-cell lymphoma, however, the mechanisms by which HCV causes B-cell lymphoproliferative disorder are still unclear. Herein, we demonstrate the expression of HCV viral proteins in B-cells of HCV-infected patients and show that HCV up-regulates BCR signaling in human primary B-cells. HCV nonstructural protein NS3/4A interacts with CHK2 and down-regulates its activity, modulating HuR posttranscriptional regulation of a network of target mRNAs associated with B-cell lymphoproliferative disorders. Interestingly, the BCR signaling pathway was found to have the largest number of transcripts with increased association with HuR and was up-regulated by NS3/4A. Our study reveals a previously unidentified role of NS3/4A in regulation of host BCR signaling during HCV infection, contributing to a better understanding of the molecular mechanisms underlying HCV-associated B-cell lymphoproliferative disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE71757 | GEO | 2015/10/14

SECONDARY ACCESSION(S): PRJNA292015

REPOSITORIES: GEO

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