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Mutations in the E2–PePHD region of hepatitis C virus type 1b in patients with hepatocellular carcinoma
Author(s) -
Bagaglio S.,
Mitri M. S.,
Lodrini S.,
Paties C.,
Cassini R.,
Bianchi G.,
Bernardi M.,
Lazzarin A.,
Morsica G.
Publication year - 2005
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2005.00589.x
Subject(s) - hepatocellular carcinoma , hccs , protein kinase r , hepatitis c virus , mutation , biology , protein kinase domain , protein kinase a , alanine , virus , medicine , virology , kinase , cancer research , amino acid , mutant , genetics , gene , mitogen activated protein kinase kinase
Summary. 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.