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Failure to detect paramyxovirus sequences in Paget's disease of bone using the polymerase chain reaction
S H Ralston1, F S Digiovine, S J Gallacher
1Molecular Immunology Group, Northern General Hospital, Edinburgh, Scotland.
Abstract:
It is widely believed that Paget's disease of bone is due to a "slow virus" infection of osteoclasts with one of the paramyxovirus group. Controversy continues to surround the identity of the virus involved, however, since at different times evidence has been presented implicating measles virus (MV), respiratory syncytial virus (RSV), and canine distemper virus (CDV) as putative infective agents. In this study we used the technique of reverse transcription and polymerase chain reaction (PCR) to screen for paramyxovirus sequences in ribonucleic acid (RNA) extracted from pagetic bone. We were able to detect viral amplification products of the appropriate size in RNA extracted from as few as 50 cells experimentally infected with a wide range of paramyxoviruses, including measles, canine distemper, parainfluenza 3, and respiratory syncytial virus, but we found no evidence of viral products in RNA extracts of affected bone from 10 consecutive patients with Paget's disease. This study fails to support the hypothesis that active infection with one of these or a related paramyxovirus is involved in the pathogenesis of Paget's disease.
Insights
This study investigated the viral cause of Paget's disease of bone. Researchers found no evidence of paramyxovirus infection in patients, failing to support the slow virus hypothesis for this bone condition.
Area of Science:
- Molecular Biology
- Virology
- Bone Diseases
Background:
- Paget's disease of bone is hypothesized to be caused by a slow paramyxovirus infection of osteoclasts.
- Previous research has implicated measles virus (MV), respiratory syncytial virus (RSV), and canine distemper virus (CDV) as potential causative agents, though evidence remains controversial.
Purpose of the Study:
- To investigate the presence of paramyxovirus sequences in bone samples from patients with Paget's disease.
- To determine if active paramyxovirus infection plays a role in the pathogenesis of Paget's disease.
Main Methods:
- Utilized reverse transcription and polymerase chain reaction (PCR) to detect paramyxovirus sequences in RNA extracted from pagetic bone.
- Established experimental models capable of detecting viral amplification products from as few as 50 infected cells across various paramyxoviruses.
Main Results:
- No evidence of viral amplification products from measles virus, canine distemper virus, parainfluenza 3, or respiratory syncytial virus was found in RNA extracts from 10 Paget's disease patients.
- The sensitive PCR method successfully detected viral sequences in experimentally infected cells, confirming the technique's efficacy.
Conclusions:
- The study fails to support the hypothesis that active infection with measles virus, respiratory syncytial virus, canine distemper virus, or related paramyxoviruses is involved in Paget's disease pathogenesis.
- Further research is needed to explore alternative etiological factors for Paget's disease of bone.