FNL team raises awareness of mouse kidney virus affecting research reproducibility

Kidney disease researchers should be on the lookout for a newly described mouse virus that appears to be relatively common and could affect the reproducibility of research involving mice that are infected but show no symptoms, according to a new study. 

“Turns out, this virus is common in wild mice and research colonies around the world and produces persistent infections even in immunocompetent mice,” said Frederick National Laboratory (FNL) Staff Pathologist Elijah Edmondson, corresponding author of the study published Oct. 5 in Veterinary Pathology.  

Microscopic images of a mouse kidney with mouse kidney parvovirus.
Kidney, MKPV ISH in immunocompetent mice. Multifocally, MKPV is detected sparsely within renal tubules in mice with an intact immune system.

FNL is now testing its mice, including those shared with other institutions, and identifying those that are infected. Initial testing of the more than 330,000 mice maintained at FNL found that about 7 percent to 8 percent were infected. 

Two microscopic images of a mouse kidney with mouse kidney parvovirus.
Kidney, MKPV ISH in immunocompromised mice. In this severely affected kidney, MKPV is detected diffusely thoughout the section of kidney and compromising the majority of nephrons. Renal tubules are dilated and lined by degenerate, MKPV positive renal epithelium.

The mouse kidney parvovirus was first described two years ago as a life-threatening infection in mice whose immune systems had been disabled for research purposes. The discovery alerted veterinary laboratories to safeguard those particular mouse populations by screening for the virus. 

But the virus has not been studied in mice whose immune systems are normal. The current research focused on two stocks of these mice, CD-1 and Swiss Webster, that are valuable for research in toxicology, aging, drug development and other areas. When infected, these mice have kidney histopathology that worsens over time. The infection does not go away and the mice are highly contagious. 

“With typical parvoviruses, you develop immunity, clear the virus, and then it’s gone,” Edmondson said. But even though these mice have healthy immune systems, the parvovirus infection persists, and infected mice can spread the disease indefinitely. 

Scientific community unaware of virus 

Jatinder Gulani, FNL veterinarian and the study’s senior author, said there is little awareness of the virus within the scientific community at large and “when talking with other institutions they do not even know how to test for it or what samples to use.” The FNL study analyzed how to best detect the virus using a polymerase chain reaction test in various samples including blood, cage droppings (urine or feces), tissues (urinary bladder or kidney) and other samples (cage swabs) from the mice’s living quarters. Kidney samples were most effective, Gulani said. 

Scientists using mouse models for research on kidney cancer and other renal diseases should be aware of the virus, Edmondson said. Reproducibility is a hallmark of science. It should be possible for research performed in one laboratory to be replicated by a second laboratory. But if mice used in one laboratory are infected but asymptomatic and mice from the second laboratory are not infected, this may affect research results. And if no one is aware of the difference, it would be impossible to correct for it. 

If the mouse kidney parvovirus spreads to immunocompromised mice, it would be fatal, Edmondson said. Many of these laboratory animals are genetically engineered, or harbor valuable human cells, or were bred over generations, making them expensive and valuable for understanding and treating human disease. 

Testing for virus is critical to contain it 

The virus first appeared at FNL in a sample received from another institution, and it was quickly eradicated from that colony of immunocompromised mice. Gulani said this raised the question of whether the virus was present in other colonies. Testing at the Frederick and Bethesda vivariums, special facilities where the mice are raised and cared for, revealed that about 7 percent to 8 percent of the total population of 330,747 mice maintained at FNL were infected.  

Fortunately, the virus is not present in majority of the vivariums, where immunocompromised mice are used for patient-derived xenograft models, Gulani said. FNL is routinely monitoring for this virus at both campuses by PCR of kidney/fecal samples obtained from the sentinels. Biological materials obtained from other institutions are tested for this virus before they are implanted in mice in a vivarium (where the virus is excluded or not present) to prevent the introduction of the virus from outside sources.   

Currently, FNL is testing all mice provided to other institutions and acknowledging if the virus is present. In FNL laboratories that create new mouse models, such as Parirokh Awasthi’s mouse modelling laboratory, all mice are tested to be sure they are virus-free, Gulani said. 

“She [Awasthi] is a source of these mice to a lot of other places, so it needs to be contained at the source level,” Gulani said. This is also true for commercial vendors who supply research mice, but most vendors do not currently certify their mice to be free of mouse kidney parvovirus, he said. This may pose a challenge for institutions that want to exclude infected mice from research projects or to eliminate the virus altogether. 

In addition to Gulani and Edmondson, other members of the FNL research team include Wang-Ting Hsieh, Josh Kramer, Matthew Breed, Melody Roelke-Parker, Julie Stephens-Devalle, Nathan Pate, Laura Bassel, Melinda Hollingshead, Baktiar Karim, Donna Butcher, Andrew Warner, and Kunio Nagashima.