Viral DNA replication-dependent DNA damage response activation during BK polyomavirus infection

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• BK polyomavirus (BKPyV) reactivation causes severe disease in transplant patients.
• The interplay between viral and host factors in BKPyV infection is not fully understood.
• BKPyV activates the host DNA damage response (DDR) to aid its replication.

Purpose of the Study:

• Identify viral components responsible for activating ATM and ATR kinases in the DDR.
• Determine the trigger for DDR activation during BKPyV infection.
• Investigate the relationship between viral replication, DDR activation, and host genome stability.

Main Methods:

• Used UV treatment, lentivirus transduction, and mutant virus infections.
• Assessed activation of ATM and ATR kinases.
• Analyzed host DNA damage in response to viral infection.

Main Results:

• Neither input virus nor large T antigen (TAg) alone activated ATM or ATR.
• DDR activation was linked to BKPyV DNA replication.
• A TAg mutant virus that did not activate DDR caused significant host DNA damage.

Conclusions:

• BKPyV DNA replication, not viral proteins, triggers DDR activation.
• BKPyV can induce host DNA damage independently of DDR activation.
• The study provides insights into polyomavirus-host interactions and genome stability.