Mouse Kidney Parvovirus: Discovery of a Novel Pathogen of Laboratory Mice and Characterization of its Impact on Research
In 2018, Mouse kidney parvovirus (MKPV) was discovered and determined to be the etiology of murine inclusion body nephropathy (IBN), a condition of previously unknown etiology that had been observed in laboratory mice for over 4 decades by pathologists. The virus was subsequently found globally in laboratory mouse colonies with a prevalence of 9%. MKPV causes a chronic infection with viral replication predominantly occurring in renal tubular epithelium and shedding in urine. In highly immunocompromised mice, IBN can progress to marked renal lesions, renal failure and mortality, whereas in immunocompetent mice the infection causes mild lesions and remains subclinical. Experimental infection studies have shown strain differences in shedding kinetics between immunocompetent inbred C57BL/6NCrl (B6) and outbred Crl:CD1(ICR) mice, and highly immunocompromised NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice, which have implication for diagnostic testing strategies of mouse colonies. To study the impact of MKPV infection on research outcomes, experimentally infected and uninfected B6 and NSG mice we used in pharmacokinetic (PK) studies of two renally excreted drugs, and infected and uninfected B6 mice were used to model chronic kidney disease (CKD) with the adenine diet model, followed by evaluation of anatomic and clinical pathology endpoints of renal structure and function. MKPV infection did not result in significant alterations of PK parameters. In the CKD model, infection significantly altered the severity of interstitial lymphoplasmacytic infiltrates and fibrosis. MKPV should be excluded from immunodeficient mouse colonies because of its potential to induce morbidity and mortality. In light of findings on its effects on the research outcome of a model of CKD in immunocompetent mice, MKPV infection may confound results of kidney disease research performed in mice, and MKPV status should be determined and reported in such studies.