Mouse encephalomyelitis virus

According to the 2020 edition of the Pharmacopoeia, section 3601 on Quality Control of Experimental Animals Used in the Production and Testing of Biological Products, there is a mandatory testing item for the quality of experimental animals intended for biological product production and testing—specifically, a requirement for negative results. This criterion is more stringent than the corresponding requirement in the 2015 edition, which only applied to microbial testing of experimental animals. Today, we will introduce Theiler's Murine Encephalomyelitis Virus (TMEV), a key topic in this context.

Laboratory animal personnel are no strangers to this virus. The mouse encephalomyelitis virus (TMEV) is one of the common pathogens affecting laboratory mice, primarily characterized by viral infection that triggers inflammation in the mice’s brain and spinal cord, accompanied by a range of neurological symptoms. TMEV is a single-stranded RNA virus belonging to the Coronaviridae family. It can also infect rats, guinea pigs, and gerbils, posing significant health risks to these animals. In severe cases of TMEV infection, mice may develop flaccid paralysis in their hind limbs. Most often, however, TMEV causes asymptomatic or latent infections within open colonies of mice. In experimental mouse populations, the presence of TMEV can interfere with the isolation and study of other viruses, as well as with investigations into their pathogenesis. For these reasons, TMEV has been designated as one of the mandatory viruses to be tested in specific-pathogen-free (SPF) mice—and it remains a frequent target for laboratory screening. This article will provide an overview of the virology and epidemiology of the mouse encephalomyelitis virus.

The origins of the mouse encephalomyelitis virus remain unclear, but the virus is closely related to bat coronaviruses and the SARS coronavirus. Bat coronaviruses were the first to be identified as associated with the mouse encephalomyelitis virus, and later, a SARS-related coronavirus—also similar to bat coronaviruses—was discovered. While these viruses exhibit certain genomic differences, they share comparable pathogenic mechanisms and symptoms, including those that lead to encephalomyelitis.

The mouse encephalomyelitis virus is primarily transmitted via respiratory droplets. When mice infected with the virus cough or sneeze, the virus spreads through saliva and exhaled air, potentially infecting other mice nearby. Additionally, the virus can also be transmitted through direct contact with infected mice's urine, saliva, feces, and other bodily fluids. In laboratory settings, the TMEV can even spread through airborne transmission to susceptible animals such as hamsters and rats. TMEV is globally prevalent and currently ranks among the most common viruses affecting laboratory mice. In China, the infection rate of TMEV in mouse populations remains high; for instance, during the 1990s, reports indicated that the infection rate in ordinary mouse colonies reached 8–15%, while in 2014, Wang Cuie and colleagues found that the antibody positivity rate in laboratory mice was 15.2% (n=325).

The pathogenic mechanism of murine encephalomyelitis virus is primarily linked to the immune response triggered by viral infection. After infecting mice, the virus enters the body via the respiratory tract and rapidly targets lung cells. As the virus replicates and spreads throughout the body, it activates the immune system, initiating a cascade of inflammatory responses that ultimately lead to damage in both the lungs and the brain. In the brain, the virus mainly infects neuronal cells, causing neuroinflammation and subsequent neuronal cell death. This neuroinflammatory response can result in a range of neurological symptoms, such as paralysis and even coma. Existing studies suggest that after intracerebral inoculation with cell-adapted virus, the virus can cross the blood-brain barrier, entering the systemic circulation and eventually leading to viremia and infection of internal organs. Notably, while the virus can persistently replicate in the gut, it is cleared from peripheral nervous system tissues within 7 to 14 days post-inoculation. Diagnosis of murine encephalomyelitis typically involves identifying both viral infection and associated clinical symptoms. Histopathological analysis allows visualization of inflammatory changes in the brain and lungs, as well as evidence of neuronal cell death. Clinically, veterinarians or researchers can assess whether a mouse has encephalomyelitis by observing its symptoms and evaluating laboratory test results.

With the rapid advancement of molecular biology, various PCR-based molecular diagnostic techniques have become crucial tools for diagnosing TMEV viral infections. PCR-based pathogen detection methods offer distinct advantages—such as high specificity, exceptional sensitivity, and rapid diagnosis—that far surpass those of conventional diagnostic approaches. Many laboratory animal quality-testing facilities in the United States and the European Union already recommend PCR technology as the gold standard for detecting pathogens in experimental animals. Meanwhile, several domestic experimental animal testing institutions have begun developing PCR-based techniques for pathogen detection in lab animals. Beyond their application in laboratory animal quality control, these advanced molecular methods can also be utilized to assess experimental animal products, vaccine inocula, and even contaminated environmental samples—boasting speed and efficiency. Notably, the Guangdong Provincial Laboratory Animal Monitoring Institute has been conducting research since 2011 on a fluorescent quantitative RT-PCR method for detecting mouse encephalomyelitis virus. Extensive validation using clinical samples has demonstrated that this newly established method exhibits high sensitivity, strong specificity, and excellent reproducibility.

Currently, there is no specific treatment available for murine encephalomyelitis. Therefore, the primary approach involves supportive care to alleviate symptoms, such as keeping the animals hydrated and providing adequate food and water. In laboratory settings, immunosuppressive agents like dexamethasone can be used to reduce inflammatory responses; however, caution is essential when administering these drugs, as overuse may lead to exacerbated infections. Preventing murine encephalomyelitis hinges on controlling the spread and transmission of the virus. In the lab, animals should be properly isolated and subjected to stringent protective measures to prevent viral contamination. Additionally, regular monitoring and health checks are crucial for promptly identifying and managing infected animals. For individuals, maintaining good hygiene practices—such as frequent handwashing and avoiding contact with the excretions of infected animals—is vital in minimizing the pathways through which the virus can spread.

In summary, the mouse encephalomyelitis virus is a common rodent virus that can significantly impact both the health of mice and laboratory research. Therefore, preventing and controlling the spread of this virus is crucial. Regarding the issue of viral transmission in experimental mice used for research, what changes should researchers consider making? We look forward to receiving your valuable insights and suggestions.

References

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