1. An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis.
- Author
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Roediger B, Lee Q, Tikoo S, Cobbin JCA, Henderson JM, Jormakka M, O'Rourke MB, Padula MP, Pinello N, Henry M, Wynne M, Santagostino SF, Brayton CF, Rasmussen L, Lisowski L, Tay SS, Harris DC, Bertram JF, Dowling JP, Bertolino P, Lai JH, Wu W, Bachovchin WW, Wong JJ, Gorrell MD, Shaban B, Holmes EC, Jolly CJ, Monette S, and Weninger W
- Subjects
- 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, Nephritis, Interstitial virology, Parvovirus isolation & purification, Parvovirus pathogenicity
- 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.)
- Published
- 2018
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