4.7 Article

Human polyomavirus BKV infection of endothelial cells results in interferon pathway induction and persistence

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PLOS PATHOGENS
卷 15, 期 1, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1007505

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  1. National Institutes of Health (NIH) [R21 AI123611]
  2. Herbert W. and Grace Boyer endowment

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Polyomavirus BKV is highly prevalent among humans. The virus establishes an asymptomatic persistent infection in the urinary system in healthy people, but uncontrolled productive infection of the virus in immunocompromised patients can lead to serious diseases. In spite of its high prevalence, our knowledge regarding key aspects of BKV polyomavirus infection remains incomplete. To determine tissue and cell type tropism of the virus, primary human epithelial cells, endothelial cells and fibroblasts isolated from the respiratory and urinary systems were tested. Results from this study demonstrated that all 9 different types of human cells were infectable by BKV polyomavirus but showed differential cellular responses. In microvascular endothelial cells from the lung and the bladder, BKV persistent infection led to prolonged viral protein expression, low yield of infectious progeny and delayed cell death, in contrast with infection in renal proximal tubular epithelial cells, a widely used cell culture model for studying productive infection of this virus. Transcriptomic profiling revealed the activation of interferon signaling and induction of multiple interferon stimulated genes in infected microvascular endothelial cells. Further investigation demonstrated production of IFN and secretion of chemokine CXCL10 by infected endothelial cells. Activation of IRF3 and STAT1 in infected endothelial cells was also confirmed. In contrast, renal proximal tubular epithelial cells failed to mount an interferon response and underwent progressive cell death. These results demonstrated that microvascular endothelial cells are able to activate interferon signaling in response to polyomavirus BKV infection. This raises the possibility that endothelial cells might provide initial immune defense against BKV infection. Our results shed light on the persistence of and immunity against infection by BKV polyomavirus. Author summary Infection by polyomavirus BKV is common and mostly harmless in healthy populations but can cause severe damages to kidney and bladder in transplant recipients. The infection by BKV usually occurs in early childhood and persists chronically in the urinary system throughout life. Our data show that this virus has the ability to infect multiple types of human cells along the respiratory and urinary tracts. Furthermore, the infection elicits an immune response in endothelial cells, the type of cells that line the inner surface of the blood vessels. These results provide insights into the distinct cellular responses displayed by different cell types that BKV encounters during infection and spread of the virus within the body, and on innate immune responses against the infection.

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