Characterization of HCV Structural Proteins Expressed in Various Animal Cells

Matsuura, Yoshiharu; Harada, Tomonari; Makimura, M; Sato, Masahiro; Aizaki, Hideki; Suzuki, Toshizo; Miyamura, Tatsuo

doi:10.1159/000150365

Cited by 26 publications

(18 citation statements)

References 14 publications

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“…2 a), which is compatible with the size of the core protein previously reported (Harada et al, 1991 ;Matsuura et al, 1994 ;Santolini et al, 1994). There was no significant difference in the levels of core protein in the liver between the C21 and C49 lines.…”

Section: Expression Of the Core Proteinsupporting

confidence: 90%

“…One of the major issues regarding the pathogenesis of HCV-associated liver lesion is whether the HCV proteins have direct effects on pathological phenotypes. Although several strategies have been used to characterize the hepatitis C viral proteins (Grakoui et al, 1993 ;Harada et al, 1991 ;Lanford et al, 1993 ;Matsuura et al, 1992Matsuura et al, , 1994Ralston et al, 1993 ;Santolini et al, 1994), the relationship between protein expression and disease phenotype has not been clarified. We previously established transgenic mouse lines in which the HCV envelope proteins are efficiently expressed in the liver (Koike et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hepatitis C virus core protein induces hepatic steatosis in transgenic mice.

Moriya

Yotsuyanagi

Shintani

et al. 1997

Journal of General Virology

589

445

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Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide, which finally leads to development of hepatocellular carcinoma. Chronic hepatitis C is characterized by several histological features in the liver which discriminate it from other forms of hepatitis : bile duct damage, lymphoid follicles and steatosis (fatty change). Little is known, however, about the role of HCV or its viral proteins in the pathogenesis of hepatitis. Recently, the core protein of HCV has been suggested to have a transcriptional regulatory function, and thereby to

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Section: Expression Of the Core Proteinsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Hepatitis C virus core protein induces hepatic steatosis in transgenic mice.

Moriya

Yotsuyanagi

Shintani

et al. 1997

Journal of General Virology

589

445

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“…DEN and JEV are both members of the Flaviviridae family, which also includes HCV (35,50). The HCV core protein shares 22 and 30% homology with the DEN and JEV core proteins within the N-terminal 50 amino acids, respectively.…”

Section: Resultsmentioning

confidence: 99%

Proteasome Activator PA28γ-Dependent Nuclear Retention and Degradation of Hepatitis C Virus Core Protein

Moriishi

Okabayashi

Nakai

et al. 2003

J Virol

143

145

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Hepatitis C virus (HCV) core protein plays an important role in the formation of the viral nucleocapsid and a regulatory protein involved in hepatocarcinogenesis. In this study, we have identified proteasome activator PA28␥ (11S regulator ␥) as an HCV core binding protein by using yeast two-hybrid system. This interaction was demonstrated not only in cell culture but also in the livers of HCV core transgenic mice. These findings are extended to human HCV infection by the observation of this interaction in liver specimens from a patient with chronic HCV infection. Neither the interaction of HCV core protein with other PA28 subtypes nor that of PA28␥ with other Flavivirus core proteins was detected. Deletion of the PA28␥-binding region from the HCV core protein or knockout of the PA28␥ gene led to the export of the HCV core protein from the nucleus to the cytoplasm. Overexpression of PA28␥ enhanced the proteolysis of the HCV core protein. Thus, the nuclear retention and stability of the HCV core protein is regulated via a PA28␥-dependent pathway through which HCV pathogenesis may be exerted.Hepatitis C virus (HCV) is the causative agent in most cases of acute and chronic non-A, non-B hepatitis (16, 51). Over 50% of patients with acute infection evolve into a chronic carrier state (26), and persistent infection frequently results in chronic hepatitis. Chronic HCV infection may lead to the development of cirrhosis and eventually hepatocellular carcinoma (21, 51). HCV belongs to the Flaviviridae family, a family that also includes Japanese encephalitis virus (JEV) and Dengue fever virus (DEN), and possesses a viral genome consisting of a single positive-strand RNA of approximately 9.6 kb and encoding approximately 3,000 amino acids in a single polypeptide (9, 58). HCV proteins are produced as a single polypeptide that is posttranslationally cleaved by host cellular peptidases and viral proteases to yield at least 10 viral proteins (7,10,12,54).A comparison of the genome structure of HCV with other flaviviruses, as well as the observation of a specific interaction of viral sense RNA with HCV core protein in cells (53, 68), suggests that the HCV core protein forms the nucleocapsid with viral genome RNA. An HCV core protein consisting of the N-terminal 191 amino acids is generated by protein cleavage by host signal peptidase(s) (37, 52). The HCV core protein is further processed into a mature core protein lacking its C-terminal hydrophobic region by either an unknown host protease (52, 65) or by a signal peptide peptidase (36). The matured core protein is retained on the endoplasmic reticulum (ER) either by an interaction with immature core protein on the ER membrane (29) or via E1 envelope protein (32). The C-terminal hydrophobic region between amino acids 174 and 191 is essential for HCV core protein anchoring on the ER membrane and for the signal sequence of E1 protein to translocate into the ER lumen. Core proteins truncated at the C termini are mainly localized in the nucleus and, to lesser extent, in the cytoplasm...

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“…Some in vivo studies with transgenic mice have also raised the idea of the role of HCV core expression in the induction of HCC (46). Although HCV core is mostly a cytoplasmic protein located on endoplasmic reticulum membranes and around lipid vesicles, C-terminally truncated core translocates to the nucleus, where it might exert distinct biological effects (47)(48)(49). During natural HCV infection, some reports have suggested that such truncated core might be identified in the tumor tissues of patients with HCC (50,51).…”

Section: Discussionmentioning

confidence: 99%