Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Introduction: BK Polyomavirus (BKPyV) infection is a common complication in kidney transplant recipients and can result in poor outcomes and graft failure. Currently, there is no known effective antiviral agent. This study investigated the possible antiviral effects of Interferon alpha (IFNα) and its induced protein, MxA, against BKPyV.
Methods: In vitro cell culture experiments were conducted using human primary renal proximal tubular epithelial cells (HRPTECs). We also did animal studies using Balb/c mice with unilateral kidney ischemic reperfusion injury.
Results: Our results demonstrated that IFNα effectively inhibited BKPyV in vitro and murine polyomavirus in animal models. Additionally, IFNα and MxA were found to suppress BKPyV TAg and VP1 production. Silencing MxA attenuated the antiviral efficacy of IFNα. We observed that MxA interacted with BKPyV TAg, causing it to remain in the cytosol and preventing its nuclear translocation. To determine MxA's essential domain for its antiviral activities, different mutant MxA constructs were generated. The MxA mutant K83A retained its interaction with BKPyV TAg, and its antiviral effects were intact. The MxA T103A mutant, on the other hand, abolished GTPase activity, lost its protein-protein interaction with BKPyV TAg, and lost its antiviral effect.
Conclusion: IFNα and its downstream protein, MxA, have potent antiviral properties against BKPyV. Furthermore, our findings indicate that the interaction between MxA and BKVPyV TAg plays a crucial role in determining the anti-BKPyV effects of MxA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399625 | PMC |
| http://dx.doi.org/10.1016/j.bj.2023.100682 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Suppression of cisplatin induced ATF3 expression and apoptosis by BK polyomavirus and its encoded microRNA in bladder cancer cells.
Biomed Pharmacother
May 2025
Kidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; Department of Medicine, Chang Gung University, Taoyuan 333, Taiwan. Electronic address:
Recent evidence links BK polyomavirus (BKPyV) infection to an increased risk of bladder cancer. This study investigates the role of BKPyV and its microRNA, miR-B1, in cisplatin-induced apoptosis. PCR analysis detected BKPyV DNA in 3 of 22 urothelial carcinoma (UC) samples from a non-transplant population.
View Article and Find Full Text PDFSingle-cell analysis reveals host S phase drives large T antigen expression during BK polyomavirus infection.
PLoS Pathog
December 2024
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama United States of America.
BK polyomavirus (BKPyV) is a major cause of kidney transplant failure, for which there are no antivirals. The current model is that BKPyV expresses TAg (large T antigen) early during infection, promoting cells to enter S phase where the viral DNA can access the host replication machinery. Here, we performed a single-cell analysis of viral TAg expression throughout the cell cycle to reveal that robust TAg expression required replication of the host DNA first.
View Article and Find Full Text PDFInterferon-alpha and MxA inhibit BK polyomavirus replication by interaction with polyomavirus large T antigen.
Biomed J
October 2024
Kidney Research Center, Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address:
Article Synopsis
- BK Polyomavirus (BKPyV) is a common issue for kidney transplant patients, leading to serious complications, and there are currently no effective antiviral treatments.
- The study explored how Interferon alpha (IFNα) and its induced protein MxA could potentially fight BKPyV using lab experiments and animal models.
- Results showed that IFNα successfully inhibits BKPyV and that MxA plays a key role in this process by interacting with BKPyV TAg, affecting its localization and ultimately enhancing the antiviral effect.
The essential role of the ERK activation in large T antigen of BK polyomavirus regulated cell migration.
Virus Res
October 2023
Kidney Research Center and Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; Department of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan. Electronic address: dryctian
Recent studies have suggested that BK polyomavirus (BKPyV) may be associated with the development of urothelial carcinoma. In Merkel cell carcinoma, TAg and tAg are the major viral proteins of Merkel cell polyomavirus with oncogenic potential. In this study, we aimed to distinguish the role of TAg and tAg in cell migration.
View Article and Find Full Text PDFSingle-Cell, High-Content Microscopy Analysis of BK Polyomavirus Infection.
Microbiol Spectr
June 2023
Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA.
By adulthood, the majority of the population is persistently infected with BK polyomavirus (BKPyV). Only a subset of the population, generally transplant recipients on immunosuppressive drugs, will experience disease from BKPyV, but those who do have few treatment options and, frequently, poor outcomes, because to date there are no effective antivirals to treat or approved vaccines to prevent BKPyV. Most studies of BKPyV have been performed on bulk populations of cells, and the dynamics of infection at single-cell resolution have not been explored.
View Article and Find Full Text PDF