An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis

Area of Science:

• Veterinary Pathology
• Virology
• Genomics

Background:

• A spontaneous nephropathy with intranuclear inclusions has been observed in laboratory mice for over 40 years.
• The etiology of this kidney disease has remained elusive, though increased severity in immunodeficient mice suggested an infectious cause.

Purpose of the Study:

• To identify the causative agent of the spontaneous nephropathy in laboratory mice.
• To characterize the identified pathogen and the resulting kidney disease.
• To establish a new model for studying tubulointerstitial fibrosis.

Main Methods:

• Metagenomic analysis was employed to identify the infectious agent.
• Histopathological examination and clinical course analysis were performed.
• The distribution and transmission routes of the virus were investigated.

Main Results:

• Metagenomics identified an atypical parvovirus, termed mouse kidney parvovirus (MKPV), as the causative agent.
• MKPV is widespread in Australian and North American animal facilities, transmitted via fecal-oral or urinary-oral routes.
• The study detailed a progressive pathology from inclusions to renal failure, controlled by the adaptive immune system.

Conclusions:

• Mouse kidney parvovirus (MKPV) is identified as the cause of a prevalent nephropathy in laboratory mice.
• MKPV-induced nephropathy serves as a valuable model for investigating tubulointerstitial fibrosis mechanisms.
• This model shares molecular similarities with human chronic kidney disease, offering insights into human renal pathology.