Parvovirus genus

Experimental animals are the foundation and essential prerequisite for life science research. Their quality directly affects the accuracy and reliability of experimental results. Rats and mice are the most commonly used experimental animals. According to China's regulations on microbiological testing of laboratory animals, SPF-grade laboratory mice must be tested for minute virus of mice (MVM), while SPF-grade rats should be screened for Rat Parvovirus (RPV), specifically the Kilham Rat Virus (KRV) strain and the Toolan’s H-1 (H-1) strain. In contrast, testing protocols for mice and rats vary internationally. For instance, Charles River Laboratories in the United States specifies that mice should be tested for MVM and mouse parvovirus, while rats need to be examined for RPV-1, RPV-2, Rat Minute Virus (RMV), KRV, and H-1. Meanwhile, the Federation of European Laboratory Animal Science Associations (FELASA) mandates that mice undergo testing for MVM and mouse parvovirus (MPV), whereas rats must be tested for KRV, RMV, RPV, and H-1. As shown in the table below:

Viruses belonging to the genus Parvovirus exhibit icosahedral symmetry with no envelope. Mouse minute virus and mouse parvovirus both belong to the family Parvoviridae, within the genus Parvovirus. Mouse minute virus has a diameter of 20–25 nm and possesses only one serotype. In contrast, mouse parvovirus lacks an envelope, contains no lipids or carbohydrates, and features a robust, tightly packed structure. It is characterized by three distinct serotypes (MPV-1, MPV-2, and MPV-3), yet shares a similar non-structural protein architecture with mouse minute virus—leading to potential cross-reactivity in serological tests. Molecular analyses reveal that mouse parvovirus differs significantly from other parvoviruses found in rodents, particularly in the nucleocapsid gene region, where notable variations exist between mouse parvovirus and mouse minute virus.

Rat Parvovirus (RPV) belongs to the family Parvoviridae and the genus Parvovirus; it is a single-stranded, negative-sense DNA virus that also lacks an envelope. Like other parvoviruses, RPV can replicate autonomously without requiring any helper viruses, and it exhibits multiple serotypes. At the genomic and amino acid sequence levels, KRV is closely related to H-1 and RMV, while showing significant differences from RPV-1. Specifically, KRV shares 89.7% homology with H-1, 80.8% with MPV, 81.0% with MVM, 72.7% with RPV-1a, 90.9% with RMV-1a, 90.9% with RMV-1b, and 90.5% with RMV-1c.

The natural hosts of mouse minute virus and mouse parvovirus are laboratory mice and wild mice. Under experimental conditions, mouse minute virus can infect rats and hamsters. The virus can be isolated from the kidneys, intestines, and spleen of mice testing positive for mouse minute virus. Experimental infection of neonatal rats leads to viremia, with the virus detectable in the brain, liver, small intestine, and urine.

Mouse parvovirus is widely present in both laboratory and wild mouse populations and is highly contagious. MVM is primarily shed externally through the feces and urine of infected mice; mice already infected with MPV eliminate the virus via urine, feces, and respiratory secretions from the mouth and nose. Susceptible mice can become infected through direct or indirect contact, and MVM can also be transmitted vertically through the placenta—but it cannot spread via airborne transmission.

Rat parvovirus is present in laboratory rats, wild rats, and the natural environment, posing a serious threat to the health of experimental rats. Infection can lead to animal deaths and a decline in population reproductive rates, as well as environmental contamination. Rat feces and secretions are the primary sources of infection. RPV exhibits a high infection rate among wild rats; while adult rats often show no clinical symptoms upon infection, infected individuals can shed the virus in their feces for extended periods, contaminating feed, drinking water, and surrounding environments—and subsequently reinfecting susceptible animals, thereby enabling RPV to persist continuously within rat populations.

Under natural conditions, laboratory mice infected with MVM and MPV type 1 show no symptoms. Under experimental conditions, rats exhibit subclinical infections. When lactating hamsters are inoculated with MVM, they typically develop the disease within 5 to 8 days, leading to stunted growth, reduced body size, and, in some cases, clinical signs resembling those of Down syndrome. Rats naturally infected with RMV or RPV usually remain asymptomatic. In pregnant rats, infection with pathogenic strains of parvovirus often results in the death of part or all of the fetuses. Both KRV and H-1 viruses demonstrate high infectivity and severe pathogenicity, affecting both pregnant and non-pregnant rodents alike. Notably, KRV can be isolated from organ tissues, milk, and feces. When administered during early pregnancy, KRV infection frequently leads to fetal death or developmental abnormalities; in later stages, it may cause cerebellar damage and hepatitis in newborn pups. Pups inoculated via intraperitoneal or intracerebral routes typically succumb to the virus within 8 days. Adult rats infected with KRV, however, usually remain asymptomatic, showing no visible clinical signs.

Mice infected with MVM showed no obvious pathological changes upon gross examination. In neonatal mice, infection occasionally led to cerebellar damage, with histopathological analysis revealing necrosis of the outer germinal layer in the cerebellum and the presence of inclusion bodies at the site of infection. Adult mice, however, could develop septicemia. Type 1 MPV, along with RMV and RPV, typically do not cause histopathological lesions. KRV preferentially infects cells undergoing active mitosis; in lactating rats younger than 14 days, nuclear inclusion bodies were observed in hepatocytes and cerebellar ectodermal cells, while the liver also serves as a primary target organ for KRV. Naturally infected weaned rats exhibited hemorrhage, necrosis, and thrombosis in the testes and epididymis, accompanied by clinical signs such as scrotal cyanosis.

Parvoviruses exhibit strong resistance to environmental factors, as the virus can survive in dust and debris within ventilation systems. They frequently contaminate animal-derived materials, making biologically sourced materials such as tumors, cell lines, and infectious disease samples potential sources of contamination.

The mouse minute virus, along with viruses such as KRV and H-1, forms a group of broad-spectrum anticancer viruses that exhibit highly specific anti-tumor activity. Studies have shown that these viruses effectively inhibit the growth of various cancers, including liver cancer, gastric cancer, lung cancer, and sarcoma. Currently, countries around the world are intensively investigating their anticancer mechanisms, paving the way for innovative approaches to tumor prevention and treatment.

MVM typically causes asymptomatic, latent infections under natural conditions, with no clinical symptoms observed. In laboratory settings, MVM can infect mice, rats, and hamsters; while mice and rats usually remain clinically unaffected, hamsters are prone to developing lethal infections. Once infected, mice carrying MVM exhibit prolonged viral shedding, with the virus spreading widely throughout the body. As a result, MVM often contaminates various cell lines, leukemia models, and even transplantable tumor systems. Moreover, it can establish persistent infections in cell cultures, potentially skewing experimental outcomes in fields such as cell biology and oncology—indeed, MVM has previously been isolated from the CHO cell line. Globally, when experimental mice are tested for parvoviruses, MPV infection accounts for 77%, MVM infection for 16%, and mixed infections for 7%. Pan Jinchun’s investigation into the detection of MVM in clinical samples revealed that SPF mice showed a 0% nucleic acid detection rate, consistent with our company’s findings, while the antibody detection rate was 0.3%. In contrast, open-cage-housed mice exhibited significantly higher rates: 14.5% for nucleic acid detection and 68.3% for antibody detection.

Rat parvovirus can suppress the body's cellular immune function, leading to altered immune responses and affecting the proliferation and activity of lymphocytes. Additionally, if tumor grafts or cell lines are artificially contaminated, the virus may infect recipient cells and spread further. Rat parvovirus can contaminate biological samples such as serum, cell cultures, and embryos—particularly certain viral strains that have been shown to infect tumor cell lines, thereby inhibiting tumor cell growth. To effectively control the spread of this virus and ensure the quality of laboratory animals, multiple detection methods for RPV have been established. Among these, serological assays stand out as a crucial tool for diagnosing and identifying the virus. China's standards for laboratory animals specify four primary methods for detecting rat parvovirus: the Hemagglutination Inhibition (HI) test, Immuno-Enzyme Assay (IEA), Immunofluorescence Assay (IFA), and Enzyme-Linked Immunosorbent Assay (ELISA). Moreover, the PCR method is increasingly being adopted for parvovirus detection due to its high sensitivity and specificity.

Mouse parvovirus is widely distributed and exhibits strong resistance to environmental factors. Therefore, it is essential to strengthen disinfection measures for feed, bedding materials, equipment, and the surrounding environment, aiming to establish virus-free mouse colonies. Mouse parvovirus can interfere with tumors, cell lines, and other biological systems, so PCR testing or antibody detection in mice should be conducted before transplanting cells, tumors, or other biological products. Additionally, regular serological testing of experimental animals is required, and any incoming animals undergoing quarantine must be promptly isolated.

KRV can spread both horizontally and vertically. When purifying the mouse colony using hysterectomy and embryo transplantation, it's important to use pregnant mice free of infection. Additionally, young mice must be nursed by mothers that are KRV-negative. Only animals that test negative for antibodies after weaning can be selected for breeding purposes.

If animals testing positive for viral infections are identified, timely measures must be taken to prevent the virus from spreading through contact with objects or between animals. For materials suspected of being infected, it is recommended to sterilize them using methods such as autoclaving or low-temperature pasteurization before reuse. To minimize virus transmission, animal facilities should utilize cages equipped with filter-covered lids, reduce unnecessary human movement, and ensure standardized management and care of the animals. Additionally, viruses can survive in dust and debris within ventilation systems, so these areas should also be carefully monitored when conducting PCR tests on quarantine samples. Finally, staff members are advised not to keep rodent pets at home.

References

1. Wei Li, Wu Huiying, He Zhengming. Detection of Antibodies against Mouse Parvovirus [J]. Beijing Journal of Laboratory Animal Science, 1990, 7(1): 24-26.

2. Jacoby RO, Ball-Goodrich LJ, Besselsen DG, et al. Rodent parvovirus infections [J]. Lab Anim Sci, 1996, 46: 370-380.

3. Kilham L, Margolis G. Pathogenicity of minute virus of mice (MVM) for rats, mice and hamsters [J]. Proc Soc Exp Biol Med, 1970, 133(4): 1447-1452.

4. Tian Kegong, He Zhengming, Liu Qun, et al. Experimental Animal Epidemiology [M]. China Agricultural Press, 2015: 194-196.

5. GB14922.2-2011. Monitoring of Microbiological Levels in Laboratory Animals.

6. Wan C H, Sodelund-Venermo M, Pintel D J, et al. Molecular characterization of three newly recognized rat parvoviruses[J]. Journal of General Virology, 2002, 83: 2075-2083.

7. Xu F, Yuan W, Zhang T, et al. Simultaneous detection of 4 prototypical rat parvoviruses using the lumniex xTAG assay in laboratory animal health monitoring[J]. Journal of Virological Methods, 2017, 248: 61-65.