Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Reveals Ischemic Injury Promoting Polyomavirus Replication by DNA

Feng Yang1,2, Hui Zhang1, Xutao Chen1,3

  • 1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Journal of Medical Virology
|February 26, 2026
PubMed

Insights

Ischemic injury activates the DNA damage response pathway, increasing BK polyomavirus (BKPyV) replication. This study identifies CDK1 as a key gene, showing that inhibiting CDK1 can reduce BKPyV replication in kidney transplants.

Area of Science:

  • Virology
  • Molecular Biology
  • Transplantation Immunology

Background:

  • BK polyomavirus (BKPyV) establishes persistent infections in most adults.
  • BKPyV reactivation is a significant cause of kidney allograft failure, particularly after ischemic injury (IS).
  • The molecular mechanisms linking IS to enhanced BKPyV replication remain unclear.

Purpose of the Study:

  • To identify key molecular pathways and genes involved in IS-induced BKPyV replication.
  • To elucidate the role of the DNA damage response in viral reactivation.
  • To validate potential therapeutic targets for preventing BKPyV allograft nephropathy.

Main Methods:

  • Analysis of single-cell and bulk RNA-sequencing data from kidney injury models.
  • Bioinformatic identification of conserved pathways and hub genes in human and mouse models.
  • siRNA-mediated knockdown of candidate genes (CDK1) to assess BKPyV replication.

Main Results:

  • Ischemic injury was found to activate the DNA damage response pathway.
  • The cell cycle kinase CDK1 was identified as a conserved hub gene linking IS and viral replication.
  • CDK1 knockdown significantly inhibited BKPyV replication in experimental models.

Conclusions:

  • Ischemic injury promotes BKPyV replication by activating the DNA damage response pathway.
  • CDK1 plays a critical role in IS-mediated BKPyV replication.
  • Targeting CDK1 may offer a novel strategy to prevent BKPyV-associated allograft failure.

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