Mouse adenovirus

Mouse adenovirus infection is often asymptomatic in mouse populations, with prolonged periods of viral carriage and shedding—making it one of the key factors affecting mouse health. There are two serotypes of mouse adenovirus: the FL strain and the K87 strain. The FL strain typically causes fatal infections in nursing mice and leads to systemic infections in adult mice, affecting organs such as brown adipose tissue, cardiac muscle, adrenal glands, salivary glands, and kidneys. In contrast, the K87 strain usually results in localized, non-lethal infections primarily in the intestinal tract. The Chinese Pharmacopoeia mandates testing for eight viruses—including mouse adenovirus—in rodent-derived biological products. Moreover, this virus is also a mandatory test item for SPF-grade mice. Therefore, gaining a thorough understanding of the characteristics of mouse adenovirus is particularly crucial for institutions and professionals working with laboratory animals. Next, this article will delve deeper into the relevant properties of these two strains.

Mouse adenovirus (MAdV) belongs to the Adenoviridae family and the genus Mastadenovirus. It is an envelopment-free virus with a particle diameter of 65–80 nm, exhibiting icosahedral symmetry. Its nucleic acid consists of linear double-stranded DNA. Mouse adenovirus has two serotypes: MAdV-1 (strain FL) and MAdV-2 (strain K87). Among these, MAdV-1 infection can lead to conditions such as meningoencephalitis, endocarditis, and adrenal inflammation in neonatal mice, immunodeficient mice, and certain strains of adult mice—highlighting the central nervous system as its primary site of infection. In contrast, MAdV-2 infection typically causes diarrhea in mice but demonstrates poor growth efficiency in vitro cell cultures. The adenoviral capsid contains three major proteins: hexon (Ⅱ), penton base (Ⅲ), and fiber (Ⅳ), along with several other auxiliary proteins that play supportive roles in viral structure and function.

MAdV-1 was one of the first non-human primate adenoviruses discovered by Hartley and Rowe in 1960. Mice serve as its natural host, and the virus carried by mice can be transmitted back and forth between mice, tumor cells, and other materials. MAdV-1 is an endothelium-tropic virus, with mouse brain microvascular endothelial cells being its primary natural target for infection. The virus can spread directly through contact with urine, feces, or nasal secretions, and mice begin shedding the virus in their urine as early as 14 days post-infection—shedding that may persist for up to two years. MAdV-1 has the ability to infect virtually all tissues in mice; after intraperitoneal inoculation, the highest viral loads are typically found in the brain, spinal cord, and spleen. Moreover, the virus can cause severe illness and even death in nursing pups or immunocompromised animals, posing a particularly lethal threat even at very low doses—especially to young mice during lactation. Studies have shown that MAV-1 can induce severe disease in certain strains of adult mice, including SJL/J, C57BL/6, DBA, and CD-1, while other strains, such as BALB/c, C3H/He, and 129/J, exhibit remarkable resistance. Among these, SJL/J mice are the most susceptible. When susceptible animals are infected, they develop progressive paralysis, often leading to sudden death between days 4 and 6 post-infection. Notably, the prevalence of mouse adenovirus within mouse colonies remains relatively low; for instance, antibody positivity rates as high as 4% have been reported in conventional mouse populations. Although the infections are generally mild, infected mice can still shed the virus externally over extended periods. Our company’s testing data from the past five years (2018–2022) also reveal an extremely low detection rate for mouse adenovirus, standing at just 0.48%.

MAdV-2 was isolated by Japanese researchers Hashimoto and colleagues from the feces of apparently healthy DK1 inbred mice, and subsequently detected in wild mice as well as other laboratory mouse strains. A unidirectional cross-reactivity exists between MAdV-2 and MAdV-1: while anti-MAdV-1 serum can neutralize both MAdV-1 and MAdV-2 antigens, remarkably, anti-MAdV-2 serum only neutralizes the MAdV-2 antigen itself. Compared to MAdV-1, MAdV-2 exhibits a highly tissue-specific tropism in infected mice, primarily targeting intestinal epithelial cells—no viral presence was observed in any organs beyond the gut. Moreover, MAdV-2 spreads mainly via the gastrointestinal tract, with a lower infection rate in laboratory mouse populations than in wild mice. Importantly, mice infected with MAdV-2 do not succumb to the virus; instead, the virus can only be isolated from the intestines and feces. However, when neonatal rodents are infected with MAdV-2, it leads to developmental abnormalities, resulting in stunted growth and reduced body size. Serological data reveal that viruses related to mouse adenovirus antigens are more prevalent in laboratory rats than in mice, yet these rat infections involve distinct viral strains altogether, unrelated to those infecting mice. Notably, studies have identified nuclear inclusion bodies resembling typical adenoviral features within Syrian hamster intestinal epithelial cells, and electron microscopy confirmed the presence of numerous virus particles closely resembling classic adenoviruses inside the nuclei of these cells. Indirect fluorescent antibody assays showed that rat sera reacted specifically with MAV-2, yet no clinical signs associated with adenoviral infections were observed in these animals.

MAV-1 can cause acute and persistent infections in mice. Infected mice exhibit symptoms such as arching of the back, disheveled fur, abdominal breathing, mild ataxia, hyperreflexia, hindlimb paralysis, and neurological disorders—features closely associated with murine encephalomyelitis. MAV-1 is an endotheliotropic virus that specifically targets brain microvascular endothelial cells, leading to neurologic symptoms in infected mice, including tremors, sudden seizures, ataxia, and paralysis. When MAV-1 is used to inoculate athymic nude mice, it can induce duodenal hemorrhage and a fatal wasting disease. In susceptible animals challenged with the virus, progressive paralysis develops, culminating in sudden death between days 4 and 6 post-infection. Histopathological examination reveals focal necrosis in adipose tissue, along with hepatic necrosis characterized by neutrophil and lymphocyte infiltration within the necrotic areas. Intracellular inclusion bodies are also observed in infected cell nuclei. Additionally, vascular damage and inflammation are evident in brain tissue.

MAV-2 does not cause death in either neonatal or adult mice when administered through various routes; the virus can only be isolated from the intestines and feces. Infection of young, developing mice leads to stunted growth and reduced body size, while adult mice remain asymptomatic. Histological examination reveals no significant changes in MAV-2-infected mice. Notably, abundant basophilic intranuclear inclusion bodies are observed in the intestinal epithelial cells of asymptomatic mice.

Since mouse adenovirus can be transmitted back and forth between mice, tumor cells, and other materials, it can severely disrupt related experimental studies. The study found that after MAV-1 infection of a susceptible strain (C57BL/6), significant expression of chemokines and their receptors was observed in the central nervous system and kidneys. In contrast, in MAV-1-infected resistant mice (BALB/c), the expression of chemokines was markedly suppressed, with only MIP-2 being detectable in the central nervous system.

Timely detection and diagnosis of this virus are particularly crucial for the survival and welfare of mice. Currently, the common diagnostic methods for MAdV-1 and MAdV-2 are shown in the table below:

Mouse adenovirus has a low infection rate in laboratory mouse populations, making it relatively easy to eliminate the virus from the population. Uterine removal or embryo transplantation are effective methods for eradicating mouse adenovirus.

Research shows that murine adenovirus persists as a stable, latent infection within open-housing mouse colonies. There is no difference in susceptibility to this disease among different mouse strains, and the infection rate does not appear to vary significantly with seasonal changes. These findings suggest that, as laboratory animal facilities continue to improve and technology advances, the relationship between disease outbreaks and seasonal fluctuations may no longer be as pronounced as before. Instead, the quality of hygiene conditions has emerged as one of the key factors—and this should receive due attention from professionals working in this field going forward.

References

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2. He Zhengming, Wu Huiying, Wei Li, et al. Comparison of Methods for Adenovirus Infection and Serological Detection in Mouse Populations[J]. Beijing Journal of Laboratory Animal Science, 1988(02):16-20.

3. Du Jiangtao, Song Xiaoming, Zhou Shasang, et al. Establishment and Preliminary Application of a Fluorescent Quantitative PCR Method for Mouse Adenovirus[J]. Laboratory Animal Science, 2017, 34(03):49-54+65.

4. Tian Kegong, He Zhengming, Liu Qun, et al. Experimental Animal Epidemiology