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

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.