High levels of HCV core+1 antibodies in HCV patients with hepatocellular carcinoma

Dalagiorgou, Georgia; Vassilaki, Niki; Foka, Pelagia; Boumlic, Anissa; Kakkanas, Athanassios; Kochlios, Emmanouil; Khalili, Shirin; Aslanoglou, E.; Veletza, Stavroula; Orfanoudakis, Georges; Vassilopoulos, Dimitrios; Hadziyannis, Stephanos J.; Koskinas, John; Mavromara, Penelope

doi:10.1099/vir.0.023010-0

Cited by 30 publications

(37 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Up to date, core+1/ARFP expression has been observed in in vitro translation systems and in transfected hepatoma cells. These studies revealed expression of the core+1/ARF ORF in subtypes 1a and 1b, either through ribosomal frameshift from the core frame at codons 8-11 (F form) (Xu et al, 2001;Varaklioti et al, 2002) or through internal translation initiation at core+1/ ARF ORF codons 85/87 (S form) (Vassilaki & Mavromara, 2003;Boumlic et al, 2011). Other core+1/ARFP isoforms have also been described (Boulant et al, 2003;Baril & Brakier-Gingras, 2005).…”

mentioning

confidence: 99%

“…However, we recently observed core+1/ARFP expression in the JFH1-based bicistronic replicon system (unpublished results). Most importantly, indirect evidence, such as sequence analyses of HCV clinical isolates and higher prevalence of anti-core+1/ARFP antibodies in hepatocellular carcinoma (HCC) patients (Sobesky et al, 2007;Vassilaki & Mavromara, 2009;Dalagiorgou et al, 2011), implicates core+1/ARFP in liver cancer. Core protein has also been associated with HCC (Ahmad et al, 2011;Jahan et al, 2012) and, since the two ORFs overlap, core+1/ARFP may contribute to some of the functions attributed to the multifunctional core protein (Branch et al, 2005;Vassilaki & Mavromara, 2009).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site

Kotta‐Loizou

Vassilaki

Pissas

et al. 2013

Journal of General Virology

View full text Add to dashboard Cite

Chronic viral hepatitis C is characterized by iron accumulation in the liver, and hepcidin regulates iron absorption. Hepatitis C virus (HCV) core+1/ARFP is a novel protein produced by a second functional ORF within the core gene. Here, using reporter assays and HCV bicistronic replicons, we show that, similarly to core, core+1/ARFP decreases hepcidin expression in hepatoma cells. The activator protein 1 (AP1) binding site of the human hepcidin promoter, shown here to be relevant to basal promoter activity and to the repression by core, is essential for the downregulation by core+1/ARFP while the previously described C/EBP (CCAAT/enhancer binding protein) and STAT (signal transducer and activator of transcription) sites are not. Consistently, expression of the AP1 components c-jun and c-fos obliterated the repressive effect of core and core+1/ARFP. In conclusion, we provide evidence that core+1/ARFP downregulates AP1-mediated transcription, providing new insights into the biological role of core+1/ARFP, as well as the transcriptional modulation of hepcidin, the main regulator of iron metabolism.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site

Kotta‐Loizou

Vassilaki

Pissas

et al. 2013

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Responders were followedup for 6 months after termination of treatment and antibody titers were measured again at the week 72. Although 4 Jundishapur J Microbiol. In Press(In Press):e58294.…”

Section: Resultsmentioning

confidence: 99%

“…HCV is one of the leading causes of persistent infection in humans that can predispose to liver fibrosis and cirrhosis. There are some reports indicating that chronic hepatitis C (CHC) infection is strongly associated with hepatocellular carcinoma (HCC) (3)(4)(5)(6)(7)(8)(9). There is neither effective vaccine for immunization, nor a broadly effective treatment for HCV infection (3).Among different factors associated with chronic HCV infection, alternate reading frame protein (ARFP) or core+1 protein is one the newest ones that can promote persistent infection (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

A Decline in Anti-Core+1 Antibody Titer Occurs in Successful Treatment of Patients Infected with Hepatitis C Virus

Hashempoor¹,

Alborzi²,

Moayedi³

et al. 2018

Jundishapur J Microbiol

View full text Add to dashboard Cite

Background: Hepatitis C virus (HCV) causes one of the major chronic liver diseases (CLD). HCV-core encoding sequence possesses an overlapping open reading frame (ORF) that expresses a protein called F or core+1. Objectives: The current study aimed at assessing the presence and titer of anti-core+1 antibody (Ab) in 70 Iranian patients infected with HCV-1a, responder and non-responder groups, under combination therapy with pegylated interferon-α (PegIFN-α) plus ribavirin (RBV) using an enzyme-linked immunosorbent assay (ELISA). Methods: In the current cohort study, HCV-1a core+1 gene was amplified and cloned into vector followed by expressing in Escherichia coli and then, purified by ion exchange chromatography. The antibody titer of patients was evaluated before, during (12, 24, and 48 weeks), and 6 months after the end of therapy (ETR). Results: The seroprevalence of anti-core+1 Ab was 75.7% in pretreatment sera. The combination therapy could induce a decline in the level of anti-core+1 Ab in both groups of responders and non-responders. These changes were significant only in the responders (P = 0.003). The seroprevalence of anti-core+1 Ab had no correlation with the outcome of treatment. Conclusions: According to the current study results, HCV core+1 protein elicit a specific antibody response other than the anti-core protein antibodies. The current study data also suggested that the level of anti-core+1 antibody might be affected by the combination therapy and associated with sustained virological response (SVR). The data implied that the declining trend of anti-core+1 Abs during the treatment might be an alternative representation of the therapeutic response in Iranian population infected with HCV.

show abstract

“…The F protein is localized in the endoplasmic reticulum (ER) region, implying that it has a role in viral morphogenesis (81). Previous work suggests that the F protein is expressed in natural HCV infections (16). B and T cell mediated immune responses specific to ARFP have been detected in HCV patients (4).…”

Section: Introductionmentioning

confidence: 98%

Immunization with Recombinant Adenoviral Vectors Expressing HCV Core or F Proteins Leads to T Cells with Reduced Effector Molecules Granzyme B and IFN-γ: A Potential New Strategy for Immune Evasion in HCV Infection

et al. 2015

View full text Add to dashboard Cite

Multispecific, broad, and potent T cell responses have been correlated with viral clearance in hepatitis C virus (HCV) infection. However, the majority of infected patients develop chronic infection, suggesting that natural infection mostly leads to development of inefficient T cell immunity. Multiple mechanisms of immune modulation and evasion have been shown in HCV infection through various investigations. This study examined the generation and modulation of T cell responses against core and frameshift (F) proteins of HCV. A single immunization of mice with replication incompetent recombinant adenovirus vectors encoding for F or core antigens induces poor T cell responses and leads to generation of CD4+ and CD8+ T cells with low granzyme B (GrB) expression. These T cells have impaired GrB enzyme activity and are unable to kill peptide loaded target cells. The low intracellular expression of GrB is not due to degranulation of cytotoxic granules containing cytotoxic T cells. Addition of exogenous IL-2 in in vitro cultures leads to partial recovery of GrB production, whereas immunization with the Toll-like receptor (TLR) agonist poly I:C leads to complete restoration of GrB expression in both CD4+ and CD8+ T cells. Thus, a possible new strategy of T cell modulation is recognized wherein effector T cells are caused to be dysfunctional by HCV-derived antigens F or core, and strategies are also delineated to overcome this dysfunction. These studies are important in the investigation of prophylactic vaccine and immunotherapy strategies for HCV infection.

show abstract

High levels of HCV core+1 antibodies in HCV patients with hepatocellular carcinoma

Cited by 30 publications

References 43 publications

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site

A Decline in Anti-Core+1 Antibody Titer Occurs in Successful Treatment of Patients Infected with Hepatitis C Virus

Immunization with Recombinant Adenoviral Vectors Expressing HCV Core or F Proteins Leads to T Cells with Reduced Effector Molecules Granzyme B and IFN-γ: A Potential New Strategy for Immune Evasion in HCV Infection

Contact Info

Product

Resources

About