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On the trail of paramyxoviruses in Paget's disease of bone
Abstract:
The ultrastructural discovery of microcylindric inclusions in the nuclei and cytoplasm of osteoclasts in tissue affected by Paget's disease of bone has created a new approach. The morphologic similarity of the inclusions to viral structures has stimulated further studies involving immunocytologic techniques and in situ hybridization. Polyclonal antibodies reveal the presence of paramyxovirus antigens and measles virus and respiratory syncytial virus in pagetic osteoclasts. Monoclonal and monospecific polyclonal antibodies demonstrate paramyxovirus antigens of measles virus, simian virus (SV5), and human parainfluenza virus (PF3). In situ hybridization carried out with a 3H-labeled DNA probe, specific for the measles nucleocapsid protein, detects measles virus nucleotide sequences in the nuclei and cytoplasm of pagetic osteoclasts, confirming ultrastructural and immunocytologic findings. Surprisingly, the tritiated probe also hybridizes with a large proportion of mononucleated cells: osteoblasts, osteocytes, fibroblasts, and lymphocytes. This suggests a very wide host cell range for measles virus genomic information which, however, would appear to undergo translation only in osteoclasts. The cause-effect relation between the viral information contained by diseased bone cells and Paget's disease of bone remains to be established.
Insights
Researchers found paramyxovirus and measles virus in bone cells affected by Paget's disease. Viral genetic material was detected in various bone and immune cells, suggesting a broad host range but specific expression in diseased osteoclasts.
Area of Science:
- Bone biology
- Virology
- Cellular pathology
Background:
- Paget's disease of bone is characterized by abnormal osteoclast activity.
- Microcylindric inclusions resembling viral structures were observed in affected bone cells.
Purpose of the Study:
- To investigate the potential viral etiology of Paget's disease of bone.
- To identify specific viruses or viral antigens within affected osteoclasts.
Main Methods:
- Immunocytologic techniques using polyclonal and monoclonal antibodies.
- In situ hybridization with a measles virus-specific DNA probe.
- Ultrastructural analysis of bone tissue.
Main Results:
- Paramyxovirus and measles virus antigens were detected in pagetic osteoclasts.
- Measles virus nucleotide sequences were confirmed in osteoclasts via in situ hybridization.
- Viral genetic material was surprisingly found in various mononucleated cells, including osteoblasts and lymphocytes.
Conclusions:
- Measles virus and other paramyxoviruses are associated with Paget's disease of bone.
- Paget's disease osteoclasts contain measles virus genetic information, potentially undergoing translation.
- The broad detection of viral sequences suggests a wide host cell range for measles virus, with restricted expression in osteoclasts.