Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017:2017:3179421.
doi: 10.1155/2017/3179421. Epub 2017 Jun 27.

DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

Mankgopo Magdeline Kgatle  1 , Catherine Wendy Spearman  1 , Asgar Ali Kalla  2 , Henry Norman Hairwadzi  1
Affiliations
Review

DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

Mankgopo Magdeline Kgatle et al. Oxid Med Cell Longev. 2017.

Abstract

Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV). Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
HPV-16 DNA integrates into the human genome at the E2 open reading frame. This in turn disrupts the transcriptional activities of E2 protein that negatively regulates the expression of E6 and E7 oncoproteins. Suppression of p53/pRB by normal upregulation of E6/E7 oncoproteins agitates multiple cellular signalling pathways that promote uncontrolled growth, proliferation, differentiation, and invasion of damaged cells and ultimately HPV-induced carcinogenesis. Unceasing expression of HPV-16 E6 oncogene correlates with increased accumulation of NOX-induced ROS/RONS DNA damage that activates inflammasome multimeric complexes that stimulate several caspases and upregulation of the proinflammatory cytokines IL-1β, IL-1α, and IL-18. Activation of inflammasomes causes genomic instability leading to gene mutations and epigenetic alterations that are critical for cell transformation and neoplastic progression.
Figure 2
Figure 2
Chronic infection and inflammation occurs following repetitive cycles of HBV integration in the host genome. This results in overproduction of ROS production that generates DNA lesions, which promotes mutations and genome instability. Consequently, this activates a pool of inflammasomes (AIM2, ACS, NLRP3, and IFI16) and hepatoepigenetics via epigenetic regulators (DNMTs, TETs, HMTs, and HDMTs) that trigger aberrant transcriptional activities of hepatitis B x (HBx) protein and altered gene transcription leading to hepatocarcinogenesis.
Figure 3
Figure 3
EBV-infected cells elicit reactive oxygen species- (ROS-) induced DNA damage via activation of NADH oxidase (NOX) family NADPH oxidase. This leads to persistent infection and inflammation via activation of inflammasome IFI16 and ASC that trigger posttranscriptional modifications of viral and host genes that are critical for promoting B-cell immortalisation, malignant transformation, and subsequently EBV-related tumorigenesis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ziech D., Franco R., Pappa A., et al. The role of epigenetics in environmental and occupational carcinogenesis. Chemico-Biological Interactions. 2010;188(2):340–349. doi: 10.1016/j.cbi.2010.06.012. - DOI - PubMed
    1. Zingg J. M., Jones P. A. Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis. 1997;18(5):869–882. doi: 10.1093/carcin/18.5.869. - DOI - PubMed
    1. Ziech D., Franco R., Pappa A., Panayiotidis M. I. Reactive oxygen species (ROS)—induced genetic and epigenetic alterations in human carcinogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2011;711(1):167–173. - PubMed
    1. Butel J. S. Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis. 2000;21(3):405–426. doi: 10.1093/carcin/21.3.405. - DOI - PubMed
    1. Friedman S. L. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. The Journal of Biological Chemistry. 2000;275(4):2247–2250. doi: 10.1074/jbc.275.4.2247. - DOI - PubMed

LinkOut - more resources