Mutations in the E2-PePHD region of hepatitis C virus type 1b in patients with hepatocellular carcinoma

S. Bagaglio, M. S. De Mitri, S. Lodrini, C. Paties, R. Cassini, G. Bianchi, M. Bernardi, A. Lazzarin, Giulia Morsica

Research output: Contribution to journalArticle

Abstract

An interaction between the protein kinase (PKR)-eIF2-alpha phosphorylation homology domain (PePHD) within the E2 protein of hepatitis C virus (HCV) and cell protein kinase (PKR) may affect the control of protein synthesis and cell growth. In an attempt to investigate the genetic variability of the E2-PePHD domain in hepatocellular carcinoma (HCC). we studied sera and liver tissues from HCC patients. The partial E2-PePHD region was analysed by direct sequencing of the sera of 47 HCCs in cirrhotic livers and 31 cases of chronic active hepatitis (CAH), and tumoral and non-tumoral liver tissues from 13 HCC patients. A similar number of mutations was detected within the E2 domain in the HCC and CAH cases, but nine of the 47 HCCs (19%) showed an amino acid (aa) mutation at position 660. eight of which involved a change in the same aa (alanine instead of serine: A/S). No such mutation was detected in any of the PePHD sequences from the CAH patients: this difference was statistically significant (P = 0.008). The aa change at position 660 was also found in two sequences from tumoral but not non-tumoral tissue from the same liver. The analysis of 461 sequences obtained from GenBank supports the conclusion that the observed aa change is an infrequent event in HCV-infected patients, thus suggesting that it could be associated with HCC.

Original languageEnglish
Pages (from-to)243-250
Number of pages8
JournalJournal of Viral Hepatitis
Volume12
Issue number3
DOIs
Publication statusPublished - May 2005

Keywords

  • Chronic active hepatitis
  • E2-PePHD
  • Hepatitis C virus
  • Hepatocellular carcinoma
  • Interferon-inducible protein kinase

ASJC Scopus subject areas

  • Hepatology
  • Virology

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    Bagaglio, S., De Mitri, M. S., Lodrini, S., Paties, C., Cassini, R., Bianchi, G., Bernardi, M., Lazzarin, A., & Morsica, G. (2005). Mutations in the E2-PePHD region of hepatitis C virus type 1b in patients with hepatocellular carcinoma. Journal of Viral Hepatitis, 12(3), 243-250. https://doi.org/10.1111/j.1365-2893.2005.00589.x