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Published on: September 7, 2017
Infectivity and Shedding of Mouse Kidney Parvovirus After Oronasal Inoculation of C57BL/6, CD1, and NSG Mice
Mandy L Kain1, Rodolfo Ricart J Arbona2, Kenneth S Henderson3
1Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University; Current affiliation: Institute of Comparative Medicine, Columbia University ; ; lipmann@mskcc.org,
Abstract:
Mouse kidney parvovirus (MKPV), the etiology of murine inclusion body nephropathy, has been identified globally in mice used for research, with an estimated prevalence of 10% in academic colonies. In immunodeficient strains, MKPV causes significant morbidity and mortality, and severe renal pathology. In contrast, in immunocompetent mice, the infection is subclinical and causes minimal pathology. We investigated viral infectivity and shedding in inbred C57BL/6NCrl (B6), outbred Crl:CD1(ICR) (CD1), and highly immunocompromised NOD. Cg - Prkdc scid Il2rg tm1Wjl/SzJ (NSG) mice. Four doses, ranging from 1.16 × 10 3 to 1.16 × 10 6 viral copies per microliter, of an MKPV inoculum were administered oronasally to 3 mice per dose per mouse type. All 3 types (B6, CD1, and NSG) had persistent infection with prolonged shedding in urine and feces. Viral copy number in the urine generally increased over time, while shedding in the feces was more variable. Among the 3 populations, CD1 mice developed viral shedding in urine earliest (4 wk after inoculation) and at higher levels (greater than 1 × 10 7 viral copies per microliter). B6 mice become viruric later (7 wk after inoculation), with lesser virus shed (1 × 10 6 viral copies per microliter or less). In CD1 and B6 mice, peak urine shedding occurred at 11 to 14 wk after inoculation, after which levels gradually declined until 35 wk after inoculation (study endpoint). In contrast, NSG mice did not become viruric until 10 wk after inoculation and continued to shed large amounts of virus (greater than 1 × 107 viral copies per microliter) in urine until the study endpoint. Two commercial immunofluorescent serologic assays failed to detect serum antibodies to MKPV nonstructural protein 1 as late as 58 wk after inoculation, whereas immunohistochemistry of infected renal tissue successfully detected anti-MKPV serum antibodies. These results increase our knowledge of the biology of MKPV and have practical application for development of effective screening programs for this pathogen.
Insights
Mouse kidney parvovirus (MKPV) infects various mouse strains, causing prolonged shedding in urine and feces. Immunocompromised mice shed more virus for longer periods, impacting research models.
Area of Science:
- Virology and Immunology
- Animal Models in Research
Background:
- Mouse kidney parvovirus (MKPV) is a global pathogen in research mice, causing significant disease in immunodeficient strains.
- Prevalence is estimated at 10% in academic colonies, posing a challenge for research integrity.
- Understanding MKPV infectivity and shedding across different mouse models is crucial for disease management.
Purpose of the Study:
- To investigate the viral infectivity and shedding dynamics of MKPV in distinct mouse genetic backgrounds.
- To compare MKPV shedding patterns in immunocompetent (B6, CD1) and immunocompromised (NSG) mouse models.
- To evaluate the efficacy of diagnostic assays for MKPV detection in experimentally infected mice.
Main Methods:
- Oronasal inoculation of C57BL/6NCrl (B6), CD1, and NSG mice with varying doses of MKPV.
- Monitoring of viral shedding in urine and feces over 35 weeks post-inoculation.
- Serological testing using immunofluorescence assays and immunohistochemistry for antibody detection.
Main Results:
- All mouse types exhibited persistent MKPV infection with prolonged shedding in urine and feces.
- CD1 mice showed earliest and highest urine shedding, while NSG mice shed large viral loads later but persistently.
- Commercial serological assays failed to detect antibodies, while immunohistochemistry successfully identified infection.
Conclusions:
- MKPV establishes persistent infections across different mouse strains with strain-dependent shedding characteristics.
- Immunocompromised NSG mice are susceptible to prolonged high-level viral shedding.
- Current serological assays may be insufficient for detecting MKPV infection, necessitating alternative diagnostic approaches.
