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Detection of endogenous retrovirus antigens in NOD mouse pancreatic beta-cells
H Tsumura1, M Miyazawa, S Ogawa
1Institute of Laboratory Animals, Mie University School of Medicine, Japan.
Abstract:
We characterized C-type retroviruses expressed in the pancreatic beta-cells of non-obese diabetic (NOD) mice by immunohistochemical techniques and by inhibiting the production of viral particles using antisense oligonucleotides. Some cells in the pancreatic islets from both NOD and diabetes-resistant NOD-related mice (NON) reacted with a monoclonal antibody directed against the envelope protein(s) of polytropic viruses. On the other hand, NOD islet cells also showed strong immunoreactivity with an anti-gag protein monoclonal antibody and another anti-envelope protein(s) monoclonal antibody that is specific for xenotropic viruses. In antisense oligodeoxynucleotide inhibition assays, a xenotropic virus-specific phosphorothionate-particles antisense oligodeoxynucleotide significantly inhibited the occurrence of C-type virus particles in NOD mouse islet beta-cells. Therefore, C-type retrovirus-like particles expressed in NOD mouse pancreatic beta-cells were considered to be endogenous xenotropic virus. The expression of the xenotropic viral genome may be involved in the pathogenesis of the diabetic syndrome in NOD mice.
Insights
C-type retroviruses in pancreatic beta-cells of non-obese diabetic (NOD) mice were identified as endogenous xenotropic viruses. Their expression may contribute to the development of diabetes in NOD mice.
Area of Science:
- Immunology
- Virology
- Endocrinology
Background:
- Non-obese diabetic (NOD) mice are a model for autoimmune diabetes.
- C-type retroviruses are implicated in various diseases.
Purpose of the Study:
- To characterize C-type retroviruses in pancreatic beta-cells of NOD mice.
- To investigate the role of these viruses in diabetes pathogenesis.
Main Methods:
- Immunohistochemical analysis using monoclonal antibodies.
- Antisense oligodeoxynucleotide inhibition assays to block viral particle production.
Main Results:
- NOD islet cells showed immunoreactivity with antibodies against gag and xenotropic viral envelope proteins.
- A xenotropic virus-specific antisense oligodeoxynucleotide significantly inhibited C-type virus particle formation.
- Identified C-type retrovirus-like particles as endogenous xenotropic viruses.
Conclusions:
- Endogenous xenotropic retroviruses are expressed in NOD mouse pancreatic beta-cells.
- The expression of xenotropic viral genomes may play a role in the pathogenesis of diabetes in NOD mice.