An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis

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, JJL; Gorrell, MD; Shaban, B; Holmes, EC; Jolly, CJ; Monette, S; Weninger, W

An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis

Roediger, B Lee, Q Tikoo, S Cobbin, JCA Henderson, JM Jormakka, M O'Rourke, MB

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, JJL Gorrell, MD Shaban, B Holmes, EC Jolly, CJ Monette, S Weninger, W

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Publication Type:: Journal Article
Citation:: Cell, 2018, 175 (2), pp. 530 - 543.e24
Issue Date:: 2018-10-04

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Field	Value	Language
dc.contributor.author	Roediger, B	en_US
dc.contributor.author	Lee, Q	en_US
dc.contributor.author	Tikoo, S	en_US
dc.contributor.author	Cobbin, JCA	en_US
dc.contributor.author	Henderson, JM	en_US
dc.contributor.author	Jormakka, M	en_US
dc.contributor.author	O'Rourke, MB https://orcid.org/0000-0002-0552-2962	en_US
dc.contributor.author	Padula, MP https://orcid.org/0000-0002-8283-0643	en_US
dc.contributor.author	Pinello, N	en_US
dc.contributor.author	Henry, M	en_US
dc.contributor.author	Wynne, M	en_US
dc.contributor.author	Santagostino, SF	en_US
dc.contributor.author	Brayton, CF	en_US
dc.contributor.author	Rasmussen, L	en_US
dc.contributor.author	Lisowski, L	en_US
dc.contributor.author	Tay, SS	en_US
dc.contributor.author	Harris, DC	en_US
dc.contributor.author	Bertram, JF	en_US
dc.contributor.author	Dowling, JP	en_US
dc.contributor.author	Bertolino, P	en_US
dc.contributor.author	Lai, JH	en_US
dc.contributor.author	Wu, W	en_US
dc.contributor.author	Bachovchin, WW	en_US
dc.contributor.author	Wong, JJL	en_US
dc.contributor.author	Gorrell, MD	en_US
dc.contributor.author	Shaban, B	en_US
dc.contributor.author	Holmes, EC	en_US
dc.contributor.author	Jolly, CJ	en_US
dc.contributor.author	Monette, S	en_US
dc.contributor.author	Weninger, W	en_US
dc.date.available	2018-08-07	en_US
dc.date.issued	2018-10-04	en_US
dc.identifier.citation	Cell, 2018, 175 (2), pp. 530 - 543.e24	en_US
dc.identifier.issn	0092-8674	en_US
dc.identifier.uri	http://hdl.handle.net/10453/128211
dc.description.abstract	© 2018 Elsevier Inc. 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.	en_US
dc.relation.ispartof	Cell	en_US
dc.relation.isbasedon	10.1016/j.cell.2018.08.013	en_US
dc.subject.classification	Developmental Biology	en_US
dc.subject.mesh	Kidney	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Parvovirus	en_US
dc.subject.mesh	Parvoviridae Infections	en_US
dc.subject.mesh	Nephritis, Interstitial	en_US
dc.subject.mesh	Disease Progression	en_US
dc.subject.mesh	Fibrosis	en_US
dc.subject.mesh	North America	en_US
dc.subject.mesh	Australia	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.title	An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	175	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	175	en_US

Abstract:

© 2018 Elsevier Inc. 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/128211