Human polyomavirus modulation of the host DNA damage response

Area of Science:

• Molecular biology
• Virology
• Genomics

Background:

• The human DNA damage response (DDR) is crucial for maintaining genomic integrity.
• Human polyomaviruses (HPyVs) are oncogenic viruses that interact with host cellular machinery.
• Tumor (T) antigens expressed by HPyVs play a role in viral replication and pathogenesis.

Purpose of the Study:

• To review the interplay between disease-associated HPyVs and the human DDR.
• To highlight how HPyVs manipulate the DDR to promote viral replication and genomic instability.
• To emphasize strain-specific differences in HPyV modulation of the DDR.

Main Methods:

• Review of existing literature on HPyV-DDR interactions.
• Analysis of molecular mechanisms employed by HPyV T antigens.
• Focus on six disease-associated HPyVs and their DDR manipulation strategies.

Main Results:

• HPyVs utilize T antigens to subvert the DDR pathway.
• This subversion compromises host genomic stability, contributing to disease and cancer.
• Significant variations exist in how different HPyV strains interact with the DDR.

Conclusions:

• Understanding the HPyV-DDR interface is critical for comprehending viral pathogenesis.
• Targeting the molecular interactions between HPyVs and the DDR offers potential therapeutic avenues.
• Further research into strain-specific DDR manipulation may reveal novel treatment strategies.