Mouse Kidney Parvovirus (MKVP) (Murine Chapparvovirus - wild mice)

Prevalence
  • A novel mouse parvovirus pathogen, reported in North American and Australian animal facilities
  • >15% in North American research colonies
  • Persisting in multiple colonies for >10 years
 
Significance
  • Adverse effect of MKPV on renal function can result in increased morbidity and mortality and may compromise research results
  • MKPV-induced nephropathy holds promise as disease model enabling better understanding of fibrotic processes and pathogenesis of Chronic Kidney Disease (CKD)
 
Disease
  • Immunodeficient mice (e.g. Rag KO and NSG):
    • Kidney anatomical and functional abnormalities:
      • Macroscopic findings - firm, pale and shrunken kidneys
      • Histology - intranuclear viral inclusion bodies in renal tubular epithelium (RTE), RTE degeneration and necrosis, and interstitial fibrosis
      • Elevated serum creatinine
      • Elevated blood urea nitrogen
    • Progression to renal failure:
      • Weight loss
      • Anaemia
  • Immunocompetent mice and nude mice (lack T cells):
    • Minimal clinical illness
    • Mild/moderate nephropathy
  • Drives a loss in renal epithelial cells, expansion of activated macrophages, and development of myofibroblasts within kidney
Transmission
  • Co-housing or dirty bedding transfer
  • Via faecal-oral or urinary-oral routes (highly infectious) likely by time of weaning (3-4 weeks) when virus is highly penetrant
  • Dissemination to and/or persistence within the kidney controlled by adaptive immune system
Diagnosis
  • PCR based assay (urine, faeces, serum or kidney tissue)
Strains
  • Immunocompetent and immunodeficient strains can be infected
  • CKD in immunodeficient animals, particularly NSG and Rag mice
Duration
  • Experience kidney dysfunction for 4-5 months prior to death
Durability
  • Once established, not readily removed from host facilities - detection in a single mouse likely implies infection across colony
Screening
  • Clinically silent viruses in immunocompetent mice can have immunomodulatory effects and influence experimental outcomes - routine health monitoring is therefore warranted
Prevention and Control
  • Restock facility with MKPV-free mice
  • Rederivation - care should be taken to assess status before restarting a colony (murine parvovirus has been seen to adhere to embryos after wash steps)
  • Strict bio-exclusion practices and procedures to prevent entry or spread of viral contaminants
Reading
  • 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 Bertolino, Jack 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. An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis. Cell, 2018, 175: 1-14
  • Elizabeth F. McInnes, Mark Bennet, Mandy O’Hara, Lorna Rasmussen, Peony Fung, Philip K. Nicholls, Michael Slaven, & Robert Stevenson. Intranuclear Inclusions in Renal Tubular Epithelium in Immunodeficient Mice Strain with Antibodies for Bovine Papillomavirus Type 1 L1 Protein. Journal of Veterinary Science, 2015, 2(2):84-96
  • Megan M MacBride. Mouse Kidney Parvovirus (MKPV) – A New Mouse Pathogen. Taconic Models For Life, 2019