High prevalence of antibodies to core+1/ARF protein in HCV-infected patients with advanced cirrhosis

Kassela, Katerina; Karakasiliotis, Ioannis; Charpantidis, Stefanos; Koskinas, John; Mylopoulou, Theodora; Mimidis, Konstantinos; Sarrazin, Christoph; Grammatikos, Georgios; Mavromara, Penelope

doi:10.1099/jgv.0.000851

Cited by 10 publications

(19 citation statements)

References 42 publications

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“…During acute HCV infection, seroconversion to anti-core+1 antibodies can be observed [238]. Patients with chronic HCV infection, liver cirrhosis, and hepatocellular carcinoma have many more antibodies against core+1 products than other patients, and the antibody titers correlate with the extent of liver cirrhosis [239][240][241]. These findings show that ARF/core+1 actually is expressed in chronic HCV infection of the liver, and the extent of ARF/core+1 expression (likely as overall HCV expression) in the liver correlates with the extent of liver damage.…”

Section: Expression Of the Alternative Reading Frame Arf/core+1mentioning

confidence: 99%

Hepatitis C Virus Translation Regulation

Niepmann

Gerresheim

2020

IJMS

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Translation of the hepatitis C virus (HCV) RNA genome is regulated by the internal ribosome entry site (IRES), located in the 5’-untranslated region (5′UTR) and part of the core protein coding sequence, and by the 3′UTR. The 5′UTR has some highly conserved structural regions, while others can assume different conformations. The IRES can bind to the ribosomal 40S subunit with high affinity without any other factors. Nevertheless, IRES activity is modulated by additional cis sequences in the viral genome, including the 3′UTR and the cis-acting replication element (CRE). Canonical translation initiation factors (eIFs) are involved in HCV translation initiation, including eIF3, eIF2, eIF1A, eIF5, and eIF5B. Alternatively, under stress conditions and limited eIF2-Met-tRNAiMet availability, alternative initiation factors such as eIF2D, eIF2A, and eIF5B can substitute for eIF2 to allow HCV translation even when cellular mRNA translation is downregulated. In addition, several IRES trans-acting factors (ITAFs) modulate IRES activity by building large networks of RNA-protein and protein–protein interactions, also connecting 5′- and 3′-ends of the viral RNA. Moreover, some ITAFs can act as RNA chaperones that help to position the viral AUG start codon in the ribosomal 40S subunit entry channel. Finally, the liver-specific microRNA-122 (miR-122) stimulates HCV IRES-dependent translation, most likely by stabilizing a certain structure of the IRES that is required for initiation.

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Section: Expression Of the Alternative Reading Frame Arf/core+1mentioning

confidence: 99%

Hepatitis C Virus Translation Regulation

Niepmann

Gerresheim

2020

IJMS

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“…Consecutive blood samples were obtained from the patients at the time point of before, during (12,24, and 48 weeks), and 6 months after ETR. Responders were defined as patients with no detectable HCV RNA at the ETR and at least 6 months after ETR, while non-responders were defined as patients unclear for HCV RNA at the ETR.…”

Section: Resultsmentioning

confidence: 99%

“…The detection of high levels of specific anti-core+1 antibodies in patients infected with HCV and HCC provides strong evidence that core+1 is produced during natural infection and may have a role in the progress to advanced stages of HCV liver disease (1,12,19,20). In the study by Park et al (21), it was shown that the expression of core+1 can lead to suppression of types I and III interferon (IFN) responses in hepatocytes, suggesting the important role of the core+1 in the modulation of host innate immunity by HCV.…”

Section: Introductionmentioning

confidence: 99%

“…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). This protein is produced by a frame shift at codon 11 by a minority of ribosomes that initiate translation at the HCV AUG initiator codon of HCV genome (13,14).…”

Section: Introductionmentioning

confidence: 99%

“…Cohen et al, (5) suggested no significant correlation between the presence of anti-core+1 antibody (Ab) and HCV viremia or antiviral therapy outcome, while Gao et al, (17) found a correlation between anti-core+1 Ab and the outcome of treatment in patients infected with HCV. Many studies suggested the critical role of core+1 protein in humoral response, HCV infection status (12,18) as well as outcomes (11, Copyright © 2018, Jundishapur Journal of Microbiology. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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Sero-reactivity to three distinct regions within the hepatitis C virus alternative reading frame protein (ARFP/core+1) in patients with chronic HCV genotype-3 infection

Elsheikh

McClure

Tarr

et al. 2022

Journal of General Virology

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Hepatitis C virus (HCV) infection affects more than 71 million people worldwide. The disease slowly progresses to chronic, long-term liver injury which leads to hepatocellular carcinoma (HCC) in 5 % of infections. The alternative reading frame protein (ARFP/core+1) is encoded by a sequence overlapping the HCV core gene in the +1 reading frame. Its role in hepatitis C pathogenesis and the viral life cycle is unclear, although some observers have related its production to disease progression and the development of HCC. The aim of this study was to determine whether ARFP is immunogenic in patients with chronic HCV genotype 3 infection and to assess whether sero-reactivity is associated with disease progression, particularly to HCC. Immunogenic epitopes within the protein were predicted by a bioinformatics tool, and three −20 aa length-peptides (ARFP-P1, ARFP-P2 and ARFP-P3) were synthesized and used in an avidin-biotin ARFP/core+1 peptide ELISA. Serum samples from 50 patients with chronic HCV genotype 3 infection, 50 genotype-1 patients, 50 HBV patients and 110 healthy controls were tested. Sero-reactivity to the ARFP peptides was also tested and compared in 114 chronic HCV genotype-3 patients subdivided on the basis of disease severity into non-cirrhotic, cirrhotic and HCC groups. Chronic HCV genotype-3 patients showed noticeable rates of reactivity to ARFP and core peptides. Seropositivity rates were 58% for ARFP-P1, 47 % for ARFP-P2, 5.9 % for ARFP-P3 and 100 % for C22 peptides. There was no significant difference between these seroreactivities between HCV genotype-3 patients with HCC, and HCV genotype-3 patients with and without liver cirrhosis. Patients with chronic HCV genotype-3 infection frequently produce antibodies against ARFP/core+1 protein. ARFP peptide reactivity was not associated with disease severity in patients with HCV genotype-3. These results support the conclusion that ARFP/core+1 is produced during HCV infection, but they do not confirm that antibodies to ARFP can indicate HCV disease progression.

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High prevalence of antibodies to core+1/ARF protein in HCV-infected patients with advanced cirrhosis

Cited by 10 publications

References 42 publications

Hepatitis C Virus Translation Regulation

Hepatitis C Virus Translation Regulation

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

Sero-reactivity to three distinct regions within the hepatitis C virus alternative reading frame protein (ARFP/core+1) in patients with chronic HCV genotype-3 infection

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