DNA viruses and the cellular DNA-

damage


The DNA damage response (DDR) is a key mechanism that helps cells detect DNA damage, temporarily halt the cell cycle, activate repair pathways, or trigger apoptosis if the damage is irreparable. Viral infection often triggers a DDR, reflecting a complex interaction between the viral genome and the host cell’s DNA integrity maintenance mechanisms.


DNA viruses have evolved specific strategies to either exploit or bypass these pathways to enhance their replication. Some viruses, like Simian Virus 40 (SV40), require active DNA repair pathways for optimal replication. Others, like Adenovirus, actively suppress certain DDR pathways to prevent early activation of the cell's defense mechanisms.

Key Mechanisms of Virus Interaction with DDR Pathways

The major DNA damage response pathways are controlled by three PI3K-related kinases:


  • ATM (Ataxia Telangiectasia Mutated), involved in repairing double-strand breaks.
  • ATR (ATM and Rad3-related), activated in response to single-strand DNA lesions.
  • DNA-PK (DNA-dependent protein kinase), essential for non-homologous end joining repair of double-strand breaks.

DNA viruses modulating these pathways can either stimulate their own replication by exploiting the repair mechanisms or suppress DDR to prevent cell cycle arrest or antiviral responses.

Viral Manipulation of Repair Pathways

Certain DNA viruses, such as Herpes Simplex Virus (HSV) and Adenovirus, have evolved to interfere with these mechanisms by:


  • Inducing targeted activation of DDR to facilitate viral replication.
  • Repressing specific pathways to avoid the detection of viral DNA as damaged.
  • Using viral proteins to alter the interaction between ATM, ATR, DNA-PK, and downstream effectors.

The main goal of these manipulations is to create an intracellular environment conducive to viral gene expression and replication while avoiding apoptosis or cell cycle arrest that would limit the production of new viral particles.​

Understanding how DNA viruses interact with DDR pathways is crucial for uncovering the fundamental mechanisms of viral replication and how viruses evolve to evade cellular defense responses. Identifying the molecular targets used by viruses deepens our knowledge of viral biology and the associated cellular responses.


For a more detailed explanation, please refer to the attached PDF.