DNA damage response (DDR): a link between cellular senescence and human cytomegalovirus

DNA damage response (DDR): a link between cellular senescence and human cytomegalovirus
Saba Zeighami,¹ Cobra Moradian,^2,*
1. Bachelor’s student, Microbiology group, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
2. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Introduction: The DNA damage response (DDR) signifies a signaling cascade that transpires as a consequence of DNA impairments and disrupts cellular cycle regulation. Consequently, pro-inflammatory cytokines commence to be released. DDR damage precipitates cellular senescence. Among the pathogens implicated in the phenomenon of cellular senescence, human cytomegalovirus is particularly remarkable, which has instigated inquiries into the correlation between this virus and DDR. DNA damage, by engendering a signaling cycle, culminates in the cessation of the cellular cycle and facilitates DNA repair. This mechanism harbors signals that could present as double-strand breaks (DSB) or single-stranded DNA (ssDNA), leading to a sequence of cellular reactions aimed at DNA repair. If the DNA deterioration is not fixed, the cell will eventually face apoptosis.
Methods: To develop a deep understanding of the connection between DDR's operational response and the human cytomegalovirus's role in advancing cellular senescence, we engaged in a literature assessment employing resources from Google Scholar, PubMed, and NCBI databases. Following an exhaustive examination of the pertinent review articles and the assessments and inquiries conducted, we acquired an in-depth understanding of this subject matter.
Results: Cytomegalovirus is implicated in the cellular aging of hosts, leading to DNA damage response (DDR), which pauses the cell cycle and encourages the discharge of pro-inflammatory cytokines that elevate antiviral responses. This virus employs a sequential mechanism for gene expression, and upon infection, distinct proteins, namely 72-kDa and 86-kDa IE1 and IE2, function as transcriptional regulators by interacting with cellular proteins. In this structure, the task of interferon-beta (IFN-B), stimulated by DNA damage, encourages the growth of cellular senescence.
Conclusion: The presence of Cytomegalovirus causes host cells to enter a state of senescence while activating a significant DNA damage response (DDR), stopping the cell cycle, and fostering the production of pro-inflammatory cytokines that stimulate antiviral activity. This virus expresses its genes through a cascading mechanism, and upon infection, specific proteins such as 72-kDa and 86-kDa IE1 and IE2 function as transcriptional regulators interacting with cellular proteins. In this context, the DNA damage-induced function of interferon-beta (IFN-B) facilitates the enhancement of cellular senescence.
Keywords: DNA damage response, Cellular senescence, Human Cytomegalovirus