Hepatitis C virus core protein enhances B lymphocyte proliferation

A. Alisi, C. Giannini, A. Spaziani, S. Anticoli, P. Caini, A. L. Zignego, C. Balsano

Research output: Contribution to journalArticlepeer-review

Abstract

HCV chronic infection leads to liver diseases and also to a wide range of extrahepatic disorders including benign, but pre-lymphomatous forms (mixed cryoglobulinemia) to frank hematological neoplasia (non-Hodgkin's lymphoma). Recent data showed the involvement of p53 superfamily members in the pathogenesis of different lymphatic malignancies. In fact, tymomas and a subset of non-Hodgkin's lymphomas (NHLs) express high levels of p63. Thus, we analyzed whether alterations in p53 superfamily gene expression are observable in B lymphocytes isolated from HCV-infected patients with and without lymphoproliferative disorders. We showed, by real-time PCR, a significant induction of DNp63 mRNAs in B lymphocytes obtained from HCV-positive low grade. non-Hodgkin's lymphoma patients. Since our current understanding of HCV proteins emphasizes the ability of the HCV core protein. to deregulate the expression and activity of p53-related proteins, we established different B lymphocyte cell lines (Wil2-ns, Daudi and. Ramos) stably expressing HCV core protein, in order to investigate the possible involvement of the viral protein in the upregulation of. DNp63 in B lymphocytes. The analysis of p63 family transcripts showed no transcriptional changes for the p63 TA isoforms, whereas an. increase (>5 times) of DNp63 mRNA occurred. In all cell lines, this abnormal expression was associated with a significant increase of. cell proliferation that was specifically inhibited by silencing DNp63 mRNA. These findings suggest a pathogenetic role of the HCV core in HCV-related lymphomagenesis, through the induction of DNp63's pro-proliferative effects.

Original languageEnglish
JournalDigestive and Liver Disease
Volume39
Issue numberSUPPL. 1
DOIs
Publication statusPublished - Sep 2007

Keywords

  • DNp63
  • HCV core protein
  • Lymphomagenesis
  • PI3K

ASJC Scopus subject areas

  • Gastroenterology

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