Hepatitis C virus upregulates B-cell receptor signaling: A novel mechanism for HCV-associated B-cell lymphoproliferative disorders

B. Dai, A. Y. Chen, C. P. Corkum, R. J. Peroutka, A. Landon, S. Houng, P. A. Muniandy, Y. Zhang, E. Lehrmann, K. Mazan-Mamczarz, J. Steinhardt, M. Shlyak, Q. C. Chen, K. G. Becker, F. Livak, T. I. Michalak, R. Talwani, R. B. Gartenhaus*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

B-cell receptor (BCR) signaling is essential for the development of B cells and has 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 upregulates BCR signaling in human primary B cells. HCV nonstructural protein NS3/4A interacts with CHK2 and downregulates 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 upregulated 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.

Original languageEnglish (US)
Pages (from-to)2979-2990
Number of pages12
JournalOncogene
Volume35
Issue number23
DOIs
StatePublished - Jun 9 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Dai, B., Chen, A. Y., Corkum, C. P., Peroutka, R. J., Landon, A., Houng, S., Muniandy, P. A., Zhang, Y., Lehrmann, E., Mazan-Mamczarz, K., Steinhardt, J., Shlyak, M., Chen, Q. C., Becker, K. G., Livak, F., Michalak, T. I., Talwani, R., & Gartenhaus, R. B. (2016). Hepatitis C virus upregulates B-cell receptor signaling: A novel mechanism for HCV-associated B-cell lymphoproliferative disorders. Oncogene, 35(23), 2979-2990. https://doi.org/10.1038/onc.2015.364