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Updated: May 30, 2025
A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
How human papillomavirus (HPV) targets DNA repair pathways for viral replication: from guardian to accomplice
Arushi Vats1, Laimonis Laimins1
1Department of Microbiology-Immunology, Northwestern University, Chicago, Illinois, USA.
Abstract:
SUMMARYHuman papillomaviruses (HPVs) are small DNA viruses that are responsible for significant disease burdens worldwide, including cancers of the cervix, anogenital tract, and oropharynx. HPVs infect stratified epithelia at a variety of body locations and link their productive life cycles to the differentiation of the host cell. These viruses have evolved sophisticated mechanisms to exploit cellular pathways, such as DNA damage repair (DDR), to regulate their life cycles. HPVs activate key DDR pathways such as ATM, ATR, and FA, which are critical for maintaining genomic integrity but are often dysregulated in cancers. Importantly, these DDR pathways are essential for HPV replication in undifferentiated cells and amplification upon differentiation. The ability to modulate these DDR pathways not only enables HPV persistence but also contributes to cellular transformation. In this review, we discuss the recent advances in understanding the mechanisms by which HPV manipulates the host DDR pathways and how these depend upon enhanced topoisomerase activity and R-loop formation. Furthermore, the strategies to manipulate DDR pathways utilized by high-risk HPVs are compared with those used by other DNA viruses that exhibit similarities and distinct differences.
Insights
Human papillomaviruses (HPVs) exploit DNA damage repair (DDR) pathways for replication and persistence. Understanding how HPVs manipulate DDR, topoisomerase, and R-loops is key to developing antiviral strategies.
Area of Science:
- Virology
- Molecular Biology
- Oncology
Background:
- Human papillomaviruses (HPVs) are oncogenic DNA viruses causing significant global disease burdens, including cervical and oropharyngeal cancers.
- HPVs infect stratified epithelia and link their life cycles to host cell differentiation.
- These viruses have evolved sophisticated mechanisms to exploit host cellular pathways, notably DNA damage repair (DDR) pathways.
Purpose of the Study:
- To review recent advances in understanding how HPVs manipulate host DDR pathways.
- To elucidate the roles of topoisomerase activity and R-loop formation in HPV replication.
- To compare HPV DDR manipulation strategies with those of other DNA viruses.
Main Methods:
- Review of current literature on HPV-DDR interactions.
- Analysis of mechanisms involving topoisomerase and R-loops.
- Comparative analysis of viral strategies for manipulating host DDR pathways.
Main Results:
- HPVs activate key DDR pathways (ATM, ATR, FA) essential for viral replication and amplification during host cell differentiation.
- DDR pathway modulation by HPV is crucial for viral persistence and cellular transformation.
- Enhanced topoisomerase activity and R-loop formation are critical for HPV's manipulation of DDR pathways.
Conclusions:
- HPVs intricately manipulate host DDR pathways, including ATM, ATR, and FA, for their life cycle.
- Understanding these interactions, particularly the roles of topoisomerase and R-loops, offers insights into HPV-driven cancers.
- Comparative analysis reveals both conserved and distinct strategies among DNA viruses in exploiting host DDR machinery.
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