Measles Virus RNA Detected in Paget's Disease Bone Tissue by in situ Hybridization

Abstract

SUMMARYMorphological and immunocytological studies have demonstrated the presence of paramyxovirus antigens in Paget's bone disease tissue and in particular antigens related to measles virus and respiratory syncytial virus. To examine the relationship between measles virus and Paget's bone disease we used in situ hybridization and a cloned measles virus DNA probe specific for the nucleocapsid protein to detect and locate measles virus RNA sequences in Paget's bone tissue. In five patients with the disease, measles virus RNA sequences were detected not only in 80 to 90% of the multinucleated osteoclasts where there is morphological and immunocytological evidence of measles virus activity but also in 30 to 40% of mononucleated bone cells, mainly osteoblasts, osteocytes, fibroblasts and lympho-monocytes. In contrast, no hybridization was observed in bone tissue from three control patients without signs of Paget's bone disease. These results indicate that the host cell range for measles virus in Paget's disease is more widespread than has been supposed. They also demonstrate the usefulness of the in situ hybridization method to detect viral genetic information in cells where viral antigenic activity is not detectable. These observations further support the hypothesis that measles virus is involved in the pathogenesis of Paget's bone disease.

The Epidemiology of Paget's Disease in Britain: Is the Prevalence Decreasing?

“…(9) Subsequently, antisera against measles virus and respiratory syncitial virus were applied to both pagetic osteoclasts (21) and pagetic marrow cells from long-term cultures (22) ; in each case, viral antigens were expressed. In situ hybridization techniques have demonstrated evidence of both measles virus (23) and canine distemper virus (10,24) in pagetic bone, and measles virus nucleocapsid transcripts can be detected in pagetic bone marrow mononuclear cells. (25,26) However, many of these observations have been questioned, (27,28) and a viral etiology for Paget's disease has not been confirmed.…”

Paget disease of the bone: Does it exist in Saudi Arabia?

“…Although the exact etiology of Paget disease is unknown, previous studies suggested that genetic and environmental factors may play a role in the pathogenesis 1617. Viral infection has been suggested to play a pathogenetic role 16–18. Particles resembling those of paramyxovirus and nucleic acid sequences of measles virus, respiratory syncytial virus and canine distemper virus have all been reported from pagetic bones.…”

Ultrastructure of Bone Cells in Paget's Disease of Bone

“…The nuclei do not harbor the inclusions seen in osteoclasts, although evidence of measles virus nucleocapsid transcripts has been found in osteoblasts as determined by in situ hybridization. (30) The cells are otherwise indistinguishable from osteoblasts found in normal bone. (38) …”

“…They were judged to represent defective viruses because (with the exception of two cases in one report) budding of intact virions from cell surfaces was not observed. (9) Further support for a viral origin of the inclusions has come from immunostaining of the cells with monoclonal antibodies to measles virus and respiratory syncytial virus, (29) from demonstration of measles virus RNA in pagetic bone by in situ hybridization, (30) from demonstration of measles virus nucleocapsid transcripts by reverse transcriptase and PCR in pagetic bone marrow cells and circulating mononuclear cells, (31) from demonstration of measles virus nucleocapsid sequences in pagetic bone marrow cells, (32) and from the observation that RNase removes the microtubular nuclear and cytoplasmic inclusions from pagetic bone. (10) Canine distemper virus RNA has also been found in the bone from Paget's disease patients in England.…”