An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis.

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE
    • Publication Information:
      Publication: Cambridge, Ma : Cell Press
      Original Publication: Cambridge, MIT Press.
    • Subject Terms:
      Nephritis, Interstitial/*virology ; Parvovirus/*isolation & purification ; Parvovirus/*pathogenicity; Animals ; Australia ; Disease Progression ; Female ; Fibrosis/pathology ; Fibrosis/virology ; Humans ; Kidney/metabolism ; Kidney/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Nephritis, Interstitial/physiopathology ; North America ; Parvoviridae Infections/metabolism
    • Abstract:
      The occurrence of a spontaneous nephropathy with intranuclear inclusions in laboratory mice has puzzled pathologists for over 4 decades, because its etiology remains elusive. The condition is more severe in immunodeficient animals, suggesting an infectious cause. Using metagenomics, we identify the causative agent as an atypical virus, termed "mouse kidney parvovirus" (MKPV), belonging to a divergent genus of Parvoviridae. MKPV was identified in animal facilities in Australia and North America, is transmitted via a fecal-oral or urinary-oral route, and is controlled by the adaptive immune system. Detailed analysis of the clinical course and histopathological features demonstrated a stepwise progression of pathology ranging from sporadic tubular inclusions to tubular degeneration and interstitial fibrosis and culminating in renal failure. In summary, we identify a widely distributed pathogen in laboratory mice and establish MKPV-induced nephropathy as a new tool for elucidating mechanisms of tubulointerstitial fibrosis that shares molecular features with chronic kidney disease in humans.
      (Copyright © 2018 Elsevier Inc. All rights reserved.)
    • Comments:
      Comment in: Nat Rev Nephrol. 2018 Dec;14(12):719. (PMID: 30262845)
      Comment in: Cell. 2018 Oct 4;175(2):310-311. (PMID: 30290137)
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    • Grant Information:
      P30 CA008748 United States CA NCI NIH HHS; R01 DK107309 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: Parvoviridae; chronic kidney disease; fibrosis; inclusion body nephropathy; parvovirus; tubulointerstitial fibrosis; viral metagenomics
    • Subject Terms:
      Nephropathy, Chronic Tubulointerstitial
    • Publication Date:
      Date Created: 20180918 Date Completed: 20190614 Latest Revision: 20231014
    • Publication Date:
      20231014
    • Accession Number:
      PMC6800251
    • Accession Number:
      10.1016/j.cell.2018.08.013
    • Accession Number:
      30220458