ssDNA virus, nonenveloped
Provisionally named Chapparvovirus by ICTV, genetically and antigenically distinct from Protoparvovirus (MVM, MPV).
Wild and laboratory mice are affected.
It is moderately prevalent in laboratory and wild mice.
MuCPV is likely transmitted through both feces and urine.
Clinical Signs and Lesions
Infection by MuCPV results in intranuclear inclusion bodies in renal tubular epithelial cells with variable incidence based on immune status. Intranuclear inclusion bodies of mouse renal tubular epithelium (inclusion body nephropathy, IBN) have been anecdotally observed by veterinary pathologists for more than 40 years. Their occurrence has been reported as low in both immunocompetent and immunocompromised mice. Clinical disease has only been reported in immunocompromised models.
Adult immunodeficient mice may develop chronic renal disease indicated by shrunken, pale, and pitted kidneys. Infection of immunocompromised mice varies based on level-immune dysfunction and ranges from mild IBN to intranuclear inclusions, tubular degeneration, and necrosis. Infection may also progress onto chronic renal failure with accompanying renal fibrosis. Mild, subclinical IBN has been reported in athymic nude mice with limited immune dysfunction. The most severe pathology progressing to renal failure has been associated with the presence of increased MuCPV viral DNA in severely immunocompromised models such as Rag-/-, SCID-/-, and NSG models.
Diagnosis of MuCPV is usually made using PCR performed on the kidney, feces, or environmental samples. The limited literature describing infection and disease progression indicates the ability to detect infection may be delayed. Kidneys show a persistent infection by 61 days in an endemically infected colony while consistent viremia was delayed until approximately 100 days of life.
Additionally, a survey of wild mice showed that the prevalence of infection by MuCPV increased with age. Only 5% of juveniles were infected, compared to 62% of adult mice.
Experience indicates PCR testing of environmental samples such as open-top caging environment and exhaust air dust (EAD®) of appropriate racks, feces, and kidneys are good sample types to determine the detection of MuCPV. PCR is a reliable method of detection in samples from older, breeder age mice. Urine may also be submitted from immunodeficient mice. Testing young, soiled beddingsentinels may not reliably detect the virus.
MuCPV is highly divergent from previously known mouse parvoviruses (protoparvoviruses). It is not detected by currently available serological and PCR tests for mouse parvovirus (MPV) and minute virus of mice (MVM). Serological assays specific to MuCPV have not been reported.
Interference with Research
Parvoviruses replicate in cells undergoing active division; therefore, their presence results in modification of cellular physiology. Mouse parvovirus-1 (MPV-1) infection has been associated with modification of immune function in mice, although previously identified rodent parvoviruses, such as MPV-1, have been clinically silent. The effects of MuCPV infection have not been fully described. Infection by MuCPV has shown to induce changes in rental tubular epithelial cells infrequently in immunocompetent mouse models while infection in severely immunocompetent models may progress to chronic renal failure, morbidity, and mortality.
Prevention and Treatment
MuCPV is a newly identified virus and pathobiology of the agent has not been fully described. Previously known mouse parvoviruses (e.g., MPV) have been transmissible via animal biological products such as cell lines, transplantable tumors, and blood products, which should be tested via PCR. Since MuCPV has recently been identified, biological sources for transmission of the virus have not been fully determined. Wild mice can serve as a reservoir for MuCPV, so access of wild rodents to mouse colonies and their supplies should be prevented.
Parvoviruses are generally persistent and environmentally stable. Contamination of shared equipment, supplies, and surfaces must be addressed in any effort to eliminate them. Microisolation housing, strict aseptic husbandry, and experimental procedures are critical in limiting the spread of parvoviruses within facilities. Aggressive chemical decontamination using detergents and oxidizing disinfectants is advised, along with autoclaving or cold sterilization of materials in direct contact with animals.
Response to identification of infected animals will depend on their value, possibility of replacement, research, and ability to maintain replacement animals free from infection in the future. If the virus needs to be eliminated from a research colony, depopulation, thorough cleaning and sanitization of all aspects of the animal room, and restocking are recommended. Rederivation by embryo transfer has been described in the literature. Anecdotal evidence suggests hysterectomy rederivation should be effective in removing MuCPV from infected mouse lines.
Ben Roediger et al An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis. 2018, Cell 175, 1-14, October 4, 2018.
Simon H. Williams, Xiaoyu Che, Joel A. Garcia, John D. Klena, Bohyun Lee, Dorothy Muller, Werner Ulrich, Robert M. Corrigan, Stuart Nichol, Komal Jain, W. Ian Lipkin. Viral Diversity of House Mice in New York City. American Society for Microbiology, March/April 2018, Vol.9, Issue 2.
Tung G. Phan, Beatrix Kapusinszky, Chunlin Wang, Robert K. Rose, Howard L. Lipton, Eric L. Delwart The Fecal Viral Flora of Wild Rodents. PLOS Pathogens, September 2011, Vol. 7, Issue 9.
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Elizabeth McInnes, Mark Bennett, Mandy O’Hara, Lorna Rasmussen, Peony Fung, Philip Nicholls, Michael Slaven and Robert Stevenson. Intranuclear Inclusions in Renal Tubular Epithelium in Immunodeficient Mice Stain with Antibodies for Bovine Papillomavirus Type 1 L1 Protein. Vet. Sci. 2015, 2, 84-96.
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Mouse Parvovirus Technical Sheet (Charles River website)