An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis

Ben Roediger, Quintin Lee, Shweta Tikoo, Joanna C.A. Cobbin, James M. Henderson, Mika Jormakka, Matthew B. O'Rourke, Matthew P. Padula, Natalia Pinello, Marisa Henry, Maria Wynne, Sara F. Santagostino, Cory F. Brayton, Lorna Rasmussen, Leszek Lisowski, Szun S. Tay, David C. Harris, John F. Bertram, John P. Dowling, Patrick BertolinoJack H. Lai, Wengen Wu, William W. Bachovchin, Justin J.L. Wong, Mark D. Gorrell, Babak Shaban, Edward C. Holmes, Christopher J. Jolly, Sébastien Monette, Wolfgang Weninger

Research output: Contribution to journalArticle

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. A kidney parvovirus found in multiple laboratory mouse colonies causes spontaneous nephropathy and represents a new tool for studying chronic kidney disease.

Original languageEnglish (US)
Pages (from-to)530-543.e24
JournalCell
Volume175
Issue number2
DOIs
StatePublished - Oct 4 2018

Keywords

  • Parvoviridae
  • chronic kidney disease
  • fibrosis
  • inclusion body nephropathy
  • parvovirus
  • tubulointerstitial fibrosis
  • viral metagenomics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Roediger, B., Lee, Q., Tikoo, S., Cobbin, J. C. A., Henderson, J. M., Jormakka, M., O'Rourke, M. B., Padula, M. P., Pinello, N., Henry, M., Wynne, M., Santagostino, S. F., Brayton, C. F., Rasmussen, L., Lisowski, L., Tay, S. S., Harris, D. C., Bertram, J. F., Dowling, J. P., ... Weninger, W. (2018). An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis. Cell, 175(2), 530-543.e24. https://doi.org/10.1016/j.cell.2018.08.013