Hepatitis C Virus F Protein Is a Short-Lived Protein Associated with the Endoplasmic Reticulum

Xu, Zhenming; Choi, Jinah; Lu, Wenyue; Ou, Jing-Hsiung

doi:10.1128/jvi.77.2.1578-1583.2003

Cited by 69 publications

(73 citation statements)

References 30 publications

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“…The predicted instability indices for the core11/F and core11/S proteins were 45.63 and 51.91, respectively (29). The core11/F protein synthesized in vitro or in cultured Huh7 cells has indeed been shown, in pulse-chase labeling experiments, to be a short-lived protein with a half-life of 10 min (28,31). Its degradation has been shown to be markedly inhibited by proteasome inhibitors (MG132, lactacystin).…”

Section: Biochemical Properties Of Core11 Proteinsmentioning

confidence: 98%

“…The core11/F protein of genotype 1a has been detected by various groups in the cytoplasm of human hepatoma (Huh7, HepG2) cells, in the perinuclear area, and associated with the endoplasmic reticulum (ER) membrane (28,31,74). Only one study has reported the presence of core11/F in the nucleus, in human embryonic kidney (HEK293) cells.…”

Section: Biochemical Properties Of Core11 Proteinsmentioning

confidence: 99%

“…This hypothesis is supported by the finding that the core protein negatively regulates intracellular levels of core11 (29, 60). However, the high level of instability of core11 (28,29,31) may account for difficulties isolating this protein during productive infection.…”

Section: Functional Properties Of Core11 Proteinsmentioning

confidence: 99%

“…Puromycin is an elongation inhibitor that may promote frameshifting in the presence of this region but not in its absence. Moreover, HCV-1 codons 8-11 have been shown to direct both 22/11 and 21/12 programmed ribosomal frameshifting (27,28). However, our expression studies in RRL with the HCV-1a (H) isolate, in which the A-rich region is disrupted by a G and a C at the fourth and tenth positions, respectively (A AAG AAA AAC), showed that HCV-1a (H) did not produce p16 core11/F protein (18).…”

Section: Alternative Forms Of Core11 Proteins Trans-lated By Frameshimentioning

confidence: 99%

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The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

Vassilaki

Mavromara

2009

IUBMB Life

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Hepatitis C virus (HCV) is an enveloped positive‐strand RNA virus of the Flaviviridae family. It has a genome of about 9,600 nucleotides encoding a large polyprotein (about 3,000 amino acids) that is processed by cellular and viral proteases into at least 10 structural and nonstructural viral proteins. A novel HCV protein has also been identified by our laboratory and others. This protein—known as ARFP (alternative reading frame protein), F (for frameshift) or core+1 (to indicate the position) protein ‐ is synthesized by an open reading frame overlapping the core gene at nucleotide +1 (core+1 ORF). However, almost 10 years after its discovery, we still know little of the biological role of the ARFP/F/core+1 protein. Abolishing core+1 protein production has no affect on HCV replication in cell culture or uPA‐SCID mice, suggesting that core+1 protein is probably not important for the HCV reproductive cycle. However, the detection of specific anti‐core+1 antibodies and T‐cell responses in HCV‐infected patients, as reported by many independent laboratories, provides strong evidence that this protein is produced in vivo. Furthermore, analyses of the HCV sequences isolated from patients with hepatocellular carcinoma and in vitro studies have provided strong preliminary evidence to suggest that core+1 protein plays a role in advanced liver disease and liver cancer. The available in vitro data also suggest that certain core function proteins may depend on production of the core+1 protein. We describe here the discovery of the various forms of the core+1 protein and what is currently known about the mechanisms of their production and their biochemical and functional properties. We also provide a detailed summary of the results of patient‐based research. © 2009 IUBMB IUBMB Life, 61(7): 739–752, 2009

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Section: Biochemical Properties Of Core11 Proteinsmentioning

confidence: 98%

Section: Biochemical Properties Of Core11 Proteinsmentioning

confidence: 99%

Section: Functional Properties Of Core11 Proteinsmentioning

confidence: 99%

Section: Alternative Forms Of Core11 Proteins Trans-lated By Frameshimentioning

confidence: 99%

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The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

Vassilaki

Mavromara

2009

IUBMB Life

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“…HCV structural proteins are processed and mature in close association with the ER (Lindenbach and Rice, 2005;Xu et al, 2003). When the ER is stressed by virus, calcium depletion or accumulation of misfolded proteins, it activates the unfolded protein response and triggers alterations in calcium homeostasis and secondary mitochondrial effects (Benali-Furet et al, 2005;Liberman et al, 1999;Pavio et al, 2003;Tardif et al, 2002;Tardif et al, 2005); (Gong et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Cre-estrogen receptor-mediated hepatitis C virus structural protein expression in mice

Tumurbaatar

Sun

Chan

et al. 2007

Journal of Virological Methods

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Hepatocyte apoptosis is an important feature of liver injury in hepatitis C virus (HCV) infection. However, the mechanism of apoptosis and consequences on disease progression in vivo have not been investigated fully in part due to the lack of adequate small animal models. In this study, transgenic (tg) mice were produced that express conditionally HCV structural proteins (core, E1, E2 and p7) in the liver following Cre-mediated DNA recombination. Using a novel Cre-estrogen receptor fusion protein (Cre-ER) induction strategy, tamoxifen was injected intraperitoneally (i.p.), which induced Cre nuclear translocation, transgene recombination and HCV protein expression in the liver. Hepatic expression of HCV core and envelope proteins resulted in increased hepatocyte apoptosis, detected by the TUNEL assay, between 7 and 33 days after induction. These results were confirmed by the presence of increased levels of apoptosis-associated cytokeratin 18 (CK18) in the sera of the same animals. The presence of cleaved caspase-3 and elevated levels of CHOP/GADD153 in the liver suggests an endoplasmic reticulum (ER) stress-associated apoptosis mechanism. This study suggests an in vivo correlation between HCV structural protein expression, ER stress and hepatocyte apoptosis, implicating a potentially important mechanism of HCV pathogenesis.

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Antigenic relevance of F protein in chronic hepatitis C virus infection

et al. 2004

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Hepatitis C Virus F Protein Is a Short-Lived Protein Associated with the Endoplasmic Reticulum

Cited by 69 publications

References 30 publications

The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

Cre-estrogen receptor-mediated hepatitis C virus structural protein expression in mice

Antigenic relevance of F protein in chronic hepatitis C virus infection

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