@article{1bbc422605584ace91fec41cf5122449,
title = "An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis",
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.",
keywords = "Parvoviridae, chronic kidney disease, fibrosis, inclusion body nephropathy, parvovirus, tubulointerstitial fibrosis, viral metagenomics",
author = "Ben Roediger and Quintin Lee and Shweta Tikoo and Cobbin, {Joanna C.A.} and Henderson, {James M.} and Mika Jormakka and O'Rourke, {Matthew B.} and Padula, {Matthew P.} and Natalia Pinello and Marisa Henry and Maria Wynne and Santagostino, {Sara F.} and Brayton, {Cory F.} and Lorna Rasmussen and Leszek Lisowski and Tay, {Szun S.} and Harris, {David C.} and Bertram, {John F.} and Dowling, {John P.} and Patrick Bertolino and Lai, {Jack H.} and Wengen Wu and Bachovchin, {William W.} and Wong, {Justin J.L.} and Gorrell, {Mark D.} and Babak Shaban and Holmes, {Edward C.} and Jolly, {Christopher J.} and S{\'e}bastien Monette and Wolfgang Weninger",
note = "Funding Information: We thank M. Rizk, J. Qin, A. Cooray, C. Yee, C.M. McGuffog, I. Stevanovski, L. Shaw, R. Kwan, and K. Bremner for animal husbandry and genotyping; S.J. Cook, M. Jiao, B. Crossett, J. Chen, A. Tatian, N. Keilar, A. Lay, M. Xiang, D.J. Guo, F. Kao, A. Aspland, S. Allen, K. Jahn, and T. M. Ashhurst for technical assistance; C. Hagan, A.C. Ucero, {\"O}. Ulu{\c c}kan, W.B. Baze, P.M. Treuting, D. Imai, S. Miller, C. Goldsmith, P. McKenzie, G. Lyons, D. Vanichkina, D. Tscharke, G. Zheng, F. Sierro, M. Palendira, L. Gordon, R. Jain, R. Barugahare, P. Obeidy, E. Machala, R. Bagnall, C. Stuart, N. Lipman, and R.J. Ricart Arbona for useful discussions; and L. Cavanagh and N. Littlejohn for administrative assistance. We also acknowledge technical microscopic assistance of ACMM at University of Sydney, particularly I. Kaplin, N. Gokoolparsadh, and M. Foley. We also thank R. Stevenson and M. White and the staff at Cerberus Sciences for their assistance. This work was supported by the Australian National Health and Medical Research Council (to W. Weninger, B.R., P.B., C.J.J., M.D.G., E.C.H., J.J.-L.W, and L.L), the Cancer Institute NSW (to B.R. and J.J.-L.W), and a National Cancer Institute Cancer Center Support Grant (P30 CA008748) (to S.F.S. and S.M.). M.J. was supported by a National Institute of Diabetes and Digestive and Kidney Diseases grant (R01 DK107309). E.C.H. was funded by an Australian Research Council Australian Laureate Fellowship (FL170100022). Funding Information: We thank M. Rizk, J. Qin, A. Cooray, C. Yee, C.M. McGuffog, I. Stevanovski, L. Shaw, R. Kwan, and K. Bremner for animal husbandry and genotyping; S.J. Cook, M. Jiao, B. Crossett, J. Chen, A. Tatian, N. Keilar, A. Lay, M. Xiang, D.J. Guo, F. Kao, A. Aspland, S. Allen, K. Jahn, and T. M. Ashhurst for technical assistance; C. Hagan, A.C. Ucero, {\"O}. Ulu{\c c}kan, W.B. Baze, P.M. Treuting, D. Imai, S. Miller, C. Goldsmith, P. McKenzie, G. Lyons, D. Vanichkina, D. Tscharke, G. Zheng, F. Sierro, M. Palendira, L. Gordon, R. Jain, R. Barugahare, P. Obeidy, E. Machala, R. Bagnall, C. Stuart, N. Lipman, and R.J. Ricart Arbona for useful discussions; and L. Cavanagh and N. Littlejohn for administrative assistance. We also acknowledge technical microscopic assistance of ACMM at University of Sydney, particularly I. Kaplin, N. Gokoolparsadh, and M. Foley. We also thank R. Stevenson and M. White and the staff at Cerberus Sciences for their assistance. This work was supported by the Australian National Health and Medical Research Council (to W. Weninger, B.R., P.B., C.J.J., M.D.G., E.C.H., J.J.-L.W, and L.L), the Cancer Institute NSW (to B.R. and J.J.-L.W), and a National Cancer Institute Cancer Center Support Grant ( P30 CA008748 ) (to S.F.S. and S.M.). M.J. was supported by a National Institute of Diabetes and Digestive and Kidney Diseases grant ( R01 DK107309 ). E.C.H. was funded by an Australian Research Council Australian Laureate Fellowship ( FL170100022 ). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = oct,
day = "4",
doi = "10.1016/j.cell.2018.08.013",
language = "English (US)",
volume = "175",
pages = "530--543.e24",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}