Single-cell analysis reveals host S phase drives large T antigen expression during BK polyomavirus infection

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• BK polyomavirus (BKPyV) is a significant cause of kidney transplant failure.
• No effective antiviral treatments currently exist for BKPyV infections.
• The prevailing model suggests BKPyV TAg promotes cell cycle S phase entry for viral DNA replication.

Purpose of the Study:

• To investigate the precise timing and requirements of BKPyV TAg expression throughout the host cell cycle.
• To elucidate the role of host DNA replication in supporting BKPyV replication and TAg production.
• To refine the model of polyomavirus replication, focusing on host cell cycle interactions.

Main Methods:

• Single-cell analysis of viral TAg expression across the cell cycle.
• Utilizing specific inhibitors targeting host, but not viral, replication.
• Investigating host DNA content and cell cycle regulation during BKPyV infection.

Main Results:

• Robust BKPyV TAg expression and viral production are dependent on initial host DNA replication (S phase).
• BKPyV infection induces host cell re-replication, leading to cells with >4N DNA content.
• Subsequent viral replication rounds utilize canonical host cell cycle machinery.

Conclusions:

• BKPyV replication is tightly linked to host DNA replication, particularly during induced host re-replication.
• Understanding these host-virus interactions is crucial for developing targeted antiviral therapies against BKPyV.
• The study proposes a refined model where BKPyV TAg expression and replication depend on host S phase and re-replication events.