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A Cell Culture Model of BK Polyomavirus Persistence, Genome Recombination, and Reactivation
Linbo Zhao1, Michael J Imperiale1,2
1Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Abstract:
BK polyomavirus (BKPyV) is a small nonenveloped DNA virus that establishes a ubiquitous, asymptomatic, and lifelong persistent infection in at least 80% of the world's population. In some immunosuppressed transplant recipients, BKPyV reactivation causes polyomavirus-associated nephropathy and hemorrhagic cystitis. We report a novel in vitro model of BKPyV persistence and reactivation using a BKPyV natural host cell line. In this system, viral genome loads remain constant for various times after establishment of persistent infection, during which BKPyV undergoes extensive random genome recombination. Certain recombination events result in viral DNA amplification and protein expression, resulting in production of viruses with enhanced replication ability. IMPORTANCE BK polyomavirus (BKPyV) generally establishes a persistent subclinical infection in healthy individuals but can cause severe disease in transplant recipients. While an in vitro model to study acute replication exists, no practical model with which to study BKPyV persistence is currently available. We established a BKPyV persistence model in cell culture. Our model reveals that the virus can persist for various periods of time before random recombination of the viral genome leads to enhanced replication.
Insights
BK polyomavirus (BKPyV) establishes lifelong infections. A new in vitro model shows viral genome recombination during persistence can lead to reactivation and enhanced replication.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- BK polyomavirus (BKPyV) causes persistent infections in most humans.
- Reactivation in transplant recipients can lead to severe nephropathy and cystitis.
- Existing in vitro models do not adequately study BKPyV persistence.
Purpose of the Study:
- To establish a novel in vitro model for studying BKPyV persistence and reactivation.
- To investigate the mechanisms underlying BKPyV reactivation from a persistent state.
Main Methods:
- Utilized a BKPyV natural host cell line to establish a persistent infection model.
- Monitored viral genome loads and analyzed viral DNA recombination over time.
- Assessed viral DNA amplification and protein expression following recombination events.
Main Results:
- The in vitro model successfully maintained BKPyV persistence with stable viral genome loads.
- Extensive random genome recombination of BKPyV was observed during the persistent phase.
- Specific recombination events correlated with viral DNA amplification, protein expression, and enhanced replication ability.
Conclusions:
- The developed in vitro model provides a practical system for studying BKPyV persistence.
- Random genome recombination is a key mechanism driving BKPyV reactivation and enhanced replication.
- Understanding these mechanisms is crucial for managing BKPyV-associated diseases in immunosuppressed individuals.
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