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Canine distemper virus transcripts sequenced from pagetic bone
M T Gordon1, A P Mee, D C Anderson
1University of Manchester, Dept. of Cell and Structural Biology, Manchester, UK.
Abstract:
Paget's disease is a chronic disease of the skeleton which is believed to be caused by a persistent virus of the paramyxovirus family. There is still conflict as to the precise identity of the virus(es) involved in causing this disease. Our previous results using in situ hybridisation have implicated distemper as a possible cause of this disease. In order to confirm these results, we have reverse transcribed RNA from pagetic bone and have specifically amplified for distemper and measles sequences using the polymerase chain reaction (PCR) technique. We have found that 8/13 of the patients examined had distemper and 1/10 cases had measles nucleic acids sequestered within their bone cells. One individual was found to have both viruses sequestered in his bone cells. Dideoxy sequencing of the distemper virus PCR products revealed 2% base pair changes in the nucleic acid sequences relative to the Onderstpoort strain of canine distemper. We can conclude that in Paget's disease, canine distemper and possible other paramyxoviruses reside in bone cells and that the persistent nature of the virus may be due to mutations in the viral genome.
Insights
Canine distemper virus and other paramyxoviruses are found in bone cells of Paget's disease patients. Viral mutations may explain the persistent nature of this chronic skeletal disease.
Area of Science:
- Virology
- Skeletal Biology
- Genetics
Background:
- Paget's disease is a chronic skeletal disorder with an unknown viral etiology.
- Paramyxoviruses are suspected causative agents, with previous studies implicating distemper virus.
Purpose of the Study:
- To confirm the presence of distemper virus and identify other paramyxoviruses in Paget's disease bone cells.
- To investigate potential viral mutations contributing to disease persistence.
Main Methods:
- Reverse transcription of RNA from pagetic bone.
- Polymerase chain reaction (PCR) amplification for distemper and measles sequences.
- Dideoxy sequencing of PCR products.
Main Results:
- Distemper virus nucleic acids detected in 8/13 patients; measles virus in 1/10 patients.
- One patient showed evidence of both viruses.
- Sequencing revealed 2% base pair changes in distemper virus sequences compared to a reference strain.
Conclusions:
- Canine distemper and potentially other paramyxoviruses reside within bone cells in Paget's disease.
- Mutations in the viral genome may contribute to the chronic and persistent nature of the disease.