An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis

被引：89

作者：

Roediger, Ben ^{[1
]}

Lee, Quintin ^{[1
]}

Tikoo, Shweta ^{[1
]}

Cobbin, Joanna C. A. ^{[2
,3
]}

Henderson, James M. ^{[1
]}

Jormakka, Mika ^{[1
]}

O'Rourke, Matthew B. ^{[4
,5
]}

Padula, Matthew P. ^{[5
]}

Pinello, Natalia ^{[1
]}

Henry, Marisa ^{[1
,6
]}

Wynne, Maria ^{[1
,6
]}

Santagostino, Sara F. ^{[7
,22
]}

Brayton, Cory F. ^{[8
]}

Rasmussen, Lorna ^{[9
]}

Lisowski, Leszek ^{[10
,11
]}

Tay, Szun S. ^{[1
]}

Harris, David C. ^{[12
]}

Bertram, John F. ^{[13
,14
]}

Dowling, John P. ^{[15
]}

Bertolino, Patrick ^{[1
]}

Lai, Jack H. ^{[16
]}

Wu, Wengen ^{[16
]}

Bachovchin, William W. ^{[16
]}

Wong, Justin J-L ^{[1
]}

Gorrell, Mark D. ^{[1
]}

Shaban, Babak ^{[17
,18
]}

Holmes, Edward C. ^{[2
,3
]}

Jolly, Christopher J. ^{[1
]}

Monette, Sebastien ^{[7
]}

Weninger, Wolfgang ^{[1
,19
,20
,21
]}

机构：

[1] Univ Sydney, Fac Med & Hlth, Centenary Inst, Camperdown, NSW 2050, Australia

[2] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sch Life & Environm Sci, Sydney, NSW 2006, Australia

[3] Univ Sydney, Fac Med & Hlth, Sydney, NSW 2006, Australia

[4] Univ Sydney, Mass Spectrometry Core Facil, Sydney, NSW 2006, Australia

[5] Univ Technol Sydney, Prote Core Facil, Ultimo, NSW 2007, Australia

[6] Univ Sydney, Lab Anim Serv, Sydney, NSW 2006, Australia

[7] Rockefeller Univ, Ctr Comparat Med & Pathol, Mem Sloan Kettering Canc Ctr, Lab Comparat Pathol,Weill Cornell Med, New York, NY 10065 USA

[8] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA

[9] Cerberus Sci, Thebarton, SA 5031, Australia

[10] Univ Sydney, Childrens Med Res Inst, Sydney, NSW 2006, Australia

[11] Biol Threats Identificat & Countermeasure Ctr, Mil Inst Hyg & Epidemiol, PL-24100 Pulawy, Poland

[12] Univ Sydney, Ctr Transplantat & Renal Res, Westmead Inst Med Res, Sydney, NSW 2006, Australia

[13] Monash Univ, Monash Biomed Discovery Inst, Melbourne, Vic 3800, Australia

[14] Monash Univ, Dept Anat & Dev Biol, Melbourne, Vic 3800, Australia

[15] Monash Med Ctr, Dept Anat Pathol, Clayton, Vic 3168, Australia

[16] Tufts Univ, Sch Med, Sackler Sch Biomed Sci, Boston, MA 02111 USA

[17] Australian Genom Res Facil, Parkville, Vic 3000, Australia

[18] Univ Melbourne, Melbourne Integrat Genom, Parkville, Vic 3010, Australia

[19] Univ Sydney, Fac Med & Hlth, Discipline Dermatol, Sydney, NSW 2006, Australia

[20] Royal Prince Alfred Hosp, Dept Dermatol, Camperdown, NSW 2050, Australia

[21] Med Univ Vienna, Dept Dermatol, A-1090 Vienna, Austria

[22] Genentech Inc, Dept Safety Assessment, San Francisco, CA 94080 USA

来源：

CELL | 2018年 / 175卷 / 02期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

RENAL FIBROSIS; CELL; MICE; ALIGNMENT; TRANSCRIPTOME; PROGRESSION; RANGE;

D O I：

10.1016/j.cell.2018.08.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 estab- lish MKPV-induced nephropathy as a new tool for elucidating mechanisms of tubulointerstitial fibrosis that shares molecular features with chronic kidney disease in humans.

引用

页码：530 / +

页数：38

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