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

Area of Science:

• Molecular Biology
• Virology
• Cell Biology

Background:

• The DNA damage response (DDR) is a critical cellular pathway activated by DNA damage, leading to cell cycle arrest and DNA repair.
• Cellular senescence is an irreversible cell cycle arrest state, often accompanied by a senescence-associated secretory phenotype (SASP) involving inflammatory cytokine release.
• Human cytomegalovirus (HCMV) is a common pathogen implicated in cellular senescence processes.

Purpose of the Study:

• To review the intricate relationship between the DNA damage response (DDR), cellular senescence, and human cytomegalovirus (HCMV) infection.
• To provide novel perspectives on virus-induced senescence (VIS) driven by HCMV.

Main Methods:

• Literature review synthesizing existing research on DDR, senescence, and HCMV.
• Analysis of the molecular mechanisms linking DDR activation to HCMV replication and senescence induction.
• Exploration of the role of DDR in the establishment and characteristics of virus-induced senescence.

Main Results:

• DDR is essential for efficient HCMV replication, indicating a dependency of the virus on host cell DNA repair pathways.
• HCMV infection can trigger or modulate DDR signaling, contributing to cellular senescence.
• The interplay between DDR and HCMV influences the development of the senescence-associated secretory phenotype (SASP).

Conclusions:

• The DNA damage response (DDR) is a pivotal factor in both HCMV replication and the induction of cellular senescence.
• Understanding the DDR-HCMV-senescence axis offers new insights into virus-induced senescence (VIS).
• This review highlights potential therapeutic targets within the DDR pathway for managing HCMV infections and associated pathologies.