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Aleutian mink disease: puzzles and paradigms
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
Abstract:
Aleutian mink disease (AD) is a naturally occurring persistent virus infection of mink caused by the Aleutian mink disease parvovirus (ADV). The classical form of AD, which occurs in adult mink, is notable for high titers of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. In addition, there is a progressive renal disease characterized by mesangial proliferative glomerulonephritis and severe interstitial nephritis. Development of AD depends on both host and viral factors, and mink of certain genotypes fail to develop progressive disease when inoculated with low-virulence strains of virus. In newborn mink kits, ADV causes a fatal, acute interstitial pneumonitis associated with permissive viral replication in alveolar type 2 cells, but treatment of newborn kits with anti-viral antibody aborts the acute disease and converts into one resembling the persistent infection observed in adults. In infected adult mink, ADV is sequestered as immune complexes in lymphoid organs, but actual viral replication is restricted at the level of the individual cell and can be detected in only a small population of macrophages and follicular dendritic cells. ADV infection of mink primary macrophages and the human macrophage cell line U937 is antibody dependent and leads to the production of the cytokine interleukin-6. Furthermore, levels of interleukin-6 are increased in lymph node culture supernatants from infected mink. Chronic production of interleukin-6 may promote development of the immune disorder characteristic of AD.
Insights
Aleutian mink disease (AD) is a persistent parvovirus infection in mink. Chronic interleukin-6 production, linked to ADV infection, may drive the immune disorder characteristic of this disease.
Area of Science:
- Veterinary Virology
- Immunology
- Pathology
Background:
- Aleutian mink disease (AD) is a persistent parvovirus infection in mink caused by the Aleutian mink disease parvovirus (ADV).
- The classical form of AD involves high antibody titers, hypergammaglobulinemia, plasmacytosis, immune complex disease, and progressive renal pathology.
- ADV infection in newborn kits causes fatal interstitial pneumonitis, which can be altered by antiviral antibody treatment.
Purpose of the Study:
- To investigate the role of interleukin-6 (IL-6) in the pathogenesis of Aleutian mink disease.
- To understand the cellular mechanisms of ADV replication and immune response in mink and cell lines.
Main Methods:
- Analysis of ADV infection in adult and newborn mink, including clinical signs, antibody titers, and renal pathology.
- In vitro studies using mink primary macrophages and the U937 human macrophage cell line to assess ADV replication and cytokine production.
- Measurement of interleukin-6 levels in lymph node culture supernatants from infected mink.
Main Results:
- ADV infection leads to immune complex deposition in lymphoid organs, with limited viral replication in macrophages and follicular dendritic cells.
- ADV infection of macrophages is antibody-dependent and induces the production of interleukin-6.
- Elevated interleukin-6 levels were observed in lymph node cultures from infected mink.
Conclusions:
- Chronic interleukin-6 production, stimulated by ADV infection, may contribute to the development of the immune disorder in Aleutian mink disease.
- Understanding the interplay between ADV, host immune response, and cytokine production is crucial for managing this disease.
