Hepatitis C virus F protein: A double-edged sword in the potential contribution of chronic inflammation to carcinogenesis

Kong, Jing; Deng, Xiaozhao; Wang, Zhongchan; Yang, Jingjing; Zhang, Yun; Yu, Juan

doi:10.3892/mmr_00000122

Cited by 10 publications

(11 citation statements)

References 27 publications

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“…No significant sex differences among the three groups ( p = 0.057), and also no statistical difference existed in terms of HCV RNA level and HCV genotypes between the group of HCV F-seronegative patients and the group of F-seropositivity ( p = 0.925; p = 0.077). The results are consistent with our previous research and others reports [15,17,28]. However, subjects were significantly older in the group of F-seropositive subjects than in the group of F-seronegative patients and healthy control ( p = 0.003).…”

Section: Resultssupporting

confidence: 93%

“…These findings all indicate that the presence of F antibodies may be an indicator that predicts the efficacy of antiviral treatment in patients with HCV infection. In addition, the F protein could induce type 2 T helper (Th2) cell biased cytokine response and IL-6 secretion in HCC patients [15,17]. The imbalance of Th1/Th2 responses in patients with HCV infection may contribute to the disease progression, and further, IL-6 is a proinflammatory cytokine for which increased levels can result in chronic liver inflammation, and even progression to HCC.…”

Section: Resultsmentioning

confidence: 99%

“…Secondly, the level of Core expression was also downregulated by the intracellular synthesized F protein, which has interrelated HCV RNA secondary stem-loop structure [36,38]. Our team previously found that the HCV F protein can induce the protective T-cell-mediated immune response [15]. We reveal here for the first time, the risk factors (variants in HLA-DPA1 and HLA-DPB1 ) associated with chronic HCV infection and anti-F antibody generation.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, a “new Core” protein synthesized by a genome open reading frame (ORF) shift was named alternative reading frame protein (F protein) [13,14]. It has been demonstrated that the humoral and cellular immune responses to HCV F protein in the sera of HCV-infected patients were detected, and the rate of F-seropositivity was increased along with the progression of hepatitis C [15,16,17]. Other studies also revealed that the F protein has significant effects not only on the inhibited expression of p21 but also on promoting the development of chronic hepatitis by disturbing the balance of cytokine secretion [15,18].…”

Section: Introductionmentioning

confidence: 99%

“…It has been demonstrated that the humoral and cellular immune responses to HCV F protein in the sera of HCV-infected patients were detected, and the rate of F-seropositivity was increased along with the progression of hepatitis C [15,16,17]. Other studies also revealed that the F protein has significant effects not only on the inhibited expression of p21 but also on promoting the development of chronic hepatitis by disturbing the balance of cytokine secretion [15,18]. All these data implied that the expression of the F protein during HCV infection plays an important role in the development of persistent infection.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Variants in Human Leukocyte Antigen-DP Influence Both Hepatitis C Virus Persistence and Hepatitis C Virus F Protein Generation in the Chinese Han Population

Yue

Jiang

et al. 2014

IJMS

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Chronic hepatitis C is a serious liver disease that often results in cirrhosis or hepatocellular carcinoma. The aim of this study was to assess the association of human leukocyte antigen-DP (HLA-DP) variants with risk of chronic hepatitis C virus (HCV) or anti-F antibody generation. We selected two single nucleotide polymorphisms (SNPs) in a region including HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277534) and genotyped SNPs in 702 cases and 342 healthy controls from the Chinese population using TaqMan SNP genotyping assay. Moreover, the exon 2 of the HLA-DPA1 and HLA-DPB1 genes were amplified and determined by sequencing-based typing (SBT). The results showed that rs3077 significantly increased the risk of chronic HCV infection in additive models and dominant models (odds ratio (OR) = 1.32 and 1.53). The rs3077 also contributed to decrease the risk of anti-F antibody generation in additive models and dominant models (OR = 0.46 and 0.56). Subsequent analyses revealed the risk haplotypes (DPA1*0103-DPB1*0501 and DPA1*0103-DPB1*0201) and protective haplotypes (DPA1*0202-DPB1*0501 and DPA1*0202-DPB1*0202) to chronic HCV infection. Moreover, we also found that the haplotype of DPA1*0103-DPB1*0201 and DPA1*0202-DPB1*0202 were associated with the anti-F antibody generation. Our findings show that genetic variants in HLA-DP gene are associated with chronic HCV infection and anti-F antibody generation.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Genetic Variants in Human Leukocyte Antigen-DP Influence Both Hepatitis C Virus Persistence and Hepatitis C Virus F Protein Generation in the Chinese Han Population

Yue

Jiang

et al. 2014

IJMS

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The effects of mesenchymal stem cell mitochondrial transplantation on doxorubicin‐mediated nephrotoxicity in rats

Kubat

Özler²,

Ulger³

et al. 2020

J Biochem & Molecular Tox

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The effect of dysfunctional mitochondria in several cell pathologies has been reported in renal diseases, including diabetic nephropathy and acute kidney injury. Previous studies have reported that mitochondrial transplantation provided surprising results in myocardial and liver ischemia, as well as in Parkinson's disease. We aimed to investigate the beneficial effects of isolated mitochondria transplantation from mesenchymal stem cells (MSCs) in vivo, to mitigate renal damage that arises from doxorubicin‐mediated nephrotoxicity and its action mechanism. In this study, a kidney model of doxorubicin‐mediated nephrotoxicity was used and isolated mitochondria from MSCs were transferred to the renal cortex of rats. The findings showed that the rate of isolated mitochondria from MSCs maintains sufficient membrane integrity, and was associated with a beneficial renal therapeutic effect. Following doxorubicin‐mediated renal injury, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for five days. This study found that mitochondrial transplantation decreased cellular oxidative stress and promoted regeneration of tubular cells after renal injury (P < .001, P = .009). Moreover, mitochondrial transplantation reduced protein accumulation of tubular cells and reversed renal deficits (P = .01, P < .001). Mitochondrial transplantation increased Bcl‐2 levels, and caspase‐3 levels decreased in injured renal cells (P < .015, P < .001). Our results provide a direct link between mitochondria dysfunction and doxorubicin‐mediated nephrotoxicity and suggest a therapeutic effect of transferring isolated mitochondria obtained from MSCs against renal injury. To our knowledge, this study is the first study in the literature that showed good therapeutic effects of mitochondrial transplantation in a nephrotoxicity model, which is under‐researched.

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TBX21 polymorphisms are associated with virus persistence in hepatitis C virus infection patients from a high-risk Chinese population

Zhu

Jiang

Deng

et al. 2015

Eur J Clin Microbiol Infect Dis

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Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and the varied outcomes of the infection depend on both viral and host factors. We have demonstrated that the HCV alternate reading frame protein (F protein) is related to Th1/Th2 bias which is involved in virus persistence in chronic hepatitis C (CHC) patients. The purpose of this study was to test the hypothesis that genetic variants of TBX21 (T cell specific T-box transcription factor) were associated with the outcomes of HCV infection and F protein generation. Three single nucleotide polymorphisms (SNPs) (rs17250932, rs2074190, rs4794067) in the TBX21 gene were genotyped in a case-control study in a cohort of a high-risk group, including 354 healthy controls and 747 CHC patients (190 anti-F protein antibody seronegative patients and 557 anti-F protein antibody seropositive patients). Results showed that the rs4794067 C allele in the TBX21 promoter was significantly more common in CHC patients (OR = 1.335, 95% CI = 1.058-1.684, P = 0.015), exceptionally in anti-F protein seropositive patients (OR = 1.547, 95% CI = 1.140-2.101, P = 0.005), compared with healthy controls. And the risk effect was also significantly high in patients with HCV 1b genotype and mild fibrosis (P = 0.021, P = 0.010, respectively). Compared with the most frequent haplotype TAT, haplotype analysis showed that the distribution of TAC was significantly different between the chronic HCV carrier group and the healthy group, and so was the anti-F antibody seronegativity group and the anti-F antibody seronegativity group (all P < 0.001). Our results suggested that TBX21 variants may be involved in the etiology of this disease.

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Hepatitis C virus F protein: A double-edged sword in the potential contribution of chronic inflammation to carcinogenesis

Cited by 10 publications

References 27 publications

Genetic Variants in Human Leukocyte Antigen-DP Influence Both Hepatitis C Virus Persistence and Hepatitis C Virus F Protein Generation in the Chinese Han Population

Genetic Variants in Human Leukocyte Antigen-DP Influence Both Hepatitis C Virus Persistence and Hepatitis C Virus F Protein Generation in the Chinese Han Population

The effects of mesenchymal stem cell mitochondrial transplantation on doxorubicin‐mediated nephrotoxicity in rats

TBX21 polymorphisms are associated with virus persistence in hepatitis C virus infection patients from a high-risk Chinese population

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