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Introduction to Pathogens
Lactate dehydrogenase-elevating virus
Riley and Wroblewski (1960), in their pioneering work on early cancer diagnosis, discovered that after injecting mice with Ehrlich carcinoma cells—before any tumor growth was detectable—levels of lactate dehydrogenase in the mice's blood had already risen by 5 to 10 times. As the tumor continued to grow, LDH activity also gradually increased. Subsequently, when Riley administered an anti-tumor drug, LDH levels began to decline alongside tumor regression—but ultimately remained higher than normal. Based on these findings, they hypothesized that a virus might be responsible for this phenomenon. In 1968, Riley identified this virus (LDV) as a contaminant introduced through transplanted, cryopreserved tumors derived from 26 mice; remarkably, the virus was not an essential component of the tumor cell line itself. Because of this unique observation, the virus was named Lactate Dehydrogenase-Enhancing Virus.
Pathology
The mouse lactate dehydrogenase virus belongs to the family Arteriviridae, genus Arterivirus. Other members of this genus include the porcine reproductive and respiratory syndrome virus, equine arteritis virus, and simian hemorrhagic fever virus. Notably, the porcine reproductive and respiratory syndrome virus is most closely related to the mouse lactate dehydrogenase virus. Viral particles of this virus are typically round or elliptical in shape, with a smooth surface visible under electron microscopy, measuring an average diameter of 50–55 nm. The virus exhibits greatest stability in undiluted mouse plasma but can easily be inactivated by heat, changes in salt concentrations in suspension media, or exposure to certain chemical agents. At 4°C, the virus loses its infectivity within 32 days; however, at room temperature, infectiousness remains unchanged for up to 24 hours even in fecal or plasma samples containing the virus.
Epidemiology
This virus exhibits host specificity, infecting only mice; ARK and C58 are the susceptible strains. Infected mice carry the virus for life and can shed it externally via feces, milk, urine, or saliva. Transmission primarily occurs through contaminated tumors, cell lines, or other biological materials.
Clinical Symptoms and Impacts
Typically, mice infected with this virus do not show clinical symptoms, but they can contaminate biological materials and transplanted tumors, leading to elevated serum lactate dehydrogenase levels and potentially affecting the immune system. After mice are infected with the lactate dehydrogenase-elevating virus, various serum enzymes in their bodies exhibit distinct changes: some enzymes increase 5-10 times, others rise by 2-4 times, while a few remain unaffected. Generally speaking, an increase in tissue enzymes in plasma usually indicates cell damage; however, in mice infected with this virus, such enzyme elevation does not necessarily result from direct cell loss.
Elevated lactate dehydrogenase in mouse plasma infected with the virus
Diagnosis and Prevention
About one week after infection, the body begins producing antibodies, which exist primarily as antibody-antigen complexes. As a result, free antibodies are rarely detectable in the serum. This makes immunological diagnostic methods highly prone to false-negative results in laboratory settings, rendering them unsuitable as definitive diagnostic tools. While measuring lactate dehydrogenase levels in mice can serve as an effective method for detecting this virus, it’s important to note that mouse LDH levels may also rise due to other diseases. Therefore, molecular biology techniques should be employed to confirm the findings.
For mice already infected with the virus, timely measures such as cesarean sections and barrier isolation are necessary to cleanse the population. Since contaminated tumors, cell lines, or their bioproducts serve as the primary sources of transmission, all such related products must be tested and confirmed free of contamination before they can be used.
References
1. Chan SP, Onyekaba CO, Harty JT, Plagemann PG. 1989. Persistent infection of mice by lactate dehydrogenase-elevating virus: transient virus replication in macrophages of the spleen. Virus Res 14:317–326
2. Laboratory Animal Epidemiology
3. Margo A. Brinton. Lactate Dehydrogenase-Enhancing Virus. Laboratory Animal Science 3(1):1–11, 1986
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