Expression of hepatitis C virus core protein impairs DNA repair in human hepatoma cells

Pelt, Jos van; Severi, Tamara; Crabbé, T; Eetveldt, Annemie Van; Verslype, Chris; Roskams, Tania; Fevery, Johan

doi:10.1016/j.canlet.2003.11.035

Cited by 26 publications

(9 citation statements)

References 30 publications

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“…Hypermethylation of the Gadd45β promoter in the presence of HCV was found to be responsible for the defect and led to impaired cell cycle arrest and reduced DNA excision repair. It has also been shown that expression of the HCV core protein in hepatocellular carcinoma cells leads to an impaired ability to repair UV-induced DNA damage [ 249 ].…”

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Modulation of DNA Damage and Repair Pathways by Human Tumour Viruses

Hollingworth

Grand

2015

Viruses

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With between 10% and 15% of human cancers attributable to viral infection, there is great interest, from both a scientific and clinical viewpoint, as to how these pathogens modulate host cell functions. Seven human tumour viruses have been identified as being involved in the development of specific malignancies. It has long been known that the introduction of chromosomal aberrations is a common feature of viral infections. Intensive research over the past two decades has subsequently revealed that viruses specifically interact with cellular mechanisms responsible for the recognition and repair of DNA lesions, collectively known as the DNA damage response (DDR). These interactions can involve activation and deactivation of individual DDR pathways as well as the recruitment of specific proteins to sites of viral replication. Since the DDR has evolved to protect the genome from the accumulation of deleterious mutations, deregulation is inevitably associated with an increased risk of tumour formation. This review summarises the current literature regarding the complex relationship between known human tumour viruses and the DDR and aims to shed light on how these interactions can contribute to genomic instability and ultimately the development of human cancers.

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Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Modulation of DNA Damage and Repair Pathways by Human Tumour Viruses

Hollingworth

Grand

2015

Viruses

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“…Several gene products of human tumor viruses, such as HTLV-1 Tax, HBV HBx, HPV E6, HCV core protein, and JCV T-antigen, have been reported to induce DNA damage or repress DNA repair, which may result in genomic instability (11,28,35,44,53,64,66). Similarly, the EBV-encoded LMP1 can induce micronucleus formation, repress DNA repair, and enhance cellular sensitivity to DNA-damaging agents in a p53-independent manner (40).…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Latent Membrane Protein 1 Represses DNA Repair through the PI3K/Akt/FOXO3a Pathway in Human Epithelial Cells

Chen

Liu²,

Chang

et al. 2008

J Virol

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Latent membrane protein 1 (LMP1), an Epstein-Barr virus (EBV) oncoprotein, mimics a constitutively activated tumor necrosis factor receptor and activates various signaling pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt. LMP1 is essential for EBV-mediated B-cell transformation and is sufficient to transform several cell lines. Cellular transformation has been associated strongly with genomic instability, while DNA repair plays an important role in maintaining genomic stability. Previously, we have shown that LMP1 represses DNA repair by the C-terminal activating region 1 (CTAR1) in human epithelial cells. In the present study, we demonstrate that the PI3K/Akt pathway is required for LMP1-mediated repression of DNA repair. Through the LMP1/PI3K/Akt pathway, FOXO3a, which can induce DNA repair, is inactivated because of phosphorylation and relocalization. Expression of a constitutively active FOXO3a mutant can rescue LMP1-mediated repression of DNA repair. Furthermore, LMP1 can decrease the expression of DNA damagebinding protein 1 (DDB1), which functions in nucleotide excision repair, through the PI3K/Akt/FOXO3a pathway. LMP1-mediated repression of DNA repair is restored by DDB1, although only partially. These results suggest that LMP1 triggers the PI3K/Akt pathway to inactivate FOXO3a and decrease DDB1, which can lead to repression of DNA repair and may contribute to genomic instability in human epithelial cells.

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“…As well as inducing DNA damage, HCV can inhibit host DNA repair pathways, often through the direct interaction of viral proteins with host DDR factors. Human liver hepatocellular carcinoma cells expressing the HCV core protein are less able to repair UV-induced DNA damage than those expressing an empty vector [ 181 ]. In addition, reduced expression of the MMR genes MSH2, MLH1, MSH6 and PMS2 has also been reported in multiple cases of HCV-associated hepatocellular carcinoma [ 182 ].…”

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Activation of the DNA Damage Response by RNA Viruses

2016

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RNA viruses are a genetically diverse group of pathogens that are responsible for some of the most prevalent and lethal human diseases. Numerous viruses introduce DNA damage and genetic instability in host cells during their lifecycles and some species also manipulate components of the DNA damage response (DDR), a complex and sophisticated series of cellular pathways that have evolved to detect and repair DNA lesions. Activation and manipulation of the DDR by DNA viruses has been extensively studied. It is apparent, however, that many RNA viruses can also induce significant DNA damage, even in cases where viral replication takes place exclusively in the cytoplasm. DNA damage can contribute to the pathogenesis of RNA viruses through the triggering of apoptosis, stimulation of inflammatory immune responses and the introduction of deleterious mutations that can increase the risk of tumorigenesis. In addition, activation of DDR pathways can contribute positively to replication of viral RNA genomes. Elucidation of the interactions between RNA viruses and the DDR has provided important insights into modulation of host cell functions by these pathogens. This review summarises the current literature regarding activation and manipulation of the DDR by several medically important RNA viruses.

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Expression of hepatitis C virus core protein impairs DNA repair in human hepatoma cells

Cited by 26 publications

References 30 publications

Modulation of DNA Damage and Repair Pathways by Human Tumour Viruses

Modulation of DNA Damage and Repair Pathways by Human Tumour Viruses

Epstein-Barr Virus Latent Membrane Protein 1 Represses DNA Repair through the PI3K/Akt/FOXO3a Pathway in Human Epithelial Cells

Activation of the DNA Damage Response by RNA Viruses

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