Bone marrow mononuclear cells from patients with Paget's disease contain measles virus nucleocapsid messenger ribonucleic acid that has mutations in a specific region of the sequence.
Ultrastructural, immunocytochemical, and in situ hybridization studies have suggested that paramyxoviruses, such as measles virus (MV), are present in Pagetic osteoclasts and may contribute to the abnormality in osteoclast function. However, little additional information is known about potential viruses present in Pagetic osteoclasts. As there are increased numbers of osteoclast precursors among the marrow mononuclear cells of Paget's patients, we used the reverse transcriptase-polymerase chain reaction to amplify the nucleocapsid sequence of MV from freshly isolated bone marrow-derived mononuclear cells to examine the potential role of these viruses in cells in the osteoclast lineage. We detected MV nucleocapsid transcripts in 5 of 6 individual Paget's patients' marrow samples. MV transcripts were not detected in marrow samples from 10 normal subjects. Sequence analysis of the PCR products revealed that 1 patient had the same sequence as the Edmonston strain of MV. The remaining 4 patients had point mutations clustered between position 1360-1371 base pairs. Two of the patients exhibited identical mutations at this region. In total, 3 different point mutations were identified that resulted in amino acid substitutions. These data show that 1) unlike those from normal subjects, marrow mononuclear cells from Paget's patients express MV nucleocapsid messenger ribonucleic acid; and 2) mutations of a specific region of the MV nucleocapsid gene were present in 4 of 5 patients and suggest a persistent MV infection in Pagetic osteoclast precursors. These data further suggest that osteoclasts are infected by fusion with infected precursors.
Reddy
S V
SV
Veterans Administration Medical Center, San Antonio, Texas 78284, USA.
Singer
F R
FR
Roodman
G D
GD
D000595:Amino Acid Sequence; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology*; D002213:Capsid / Q000096:biosynthesis* / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000302:isolation & purification*; D008969:Molecular Sequence Data; D010001:Osteitis Deformans / Q000473:pathology / Q000821:virology*; D010010:Osteoclasts / Q000473:pathology / Q000821:virology*; D017354:Point Mutation; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D014758:Viral Core Proteins / Q000096:biosynthesis* / Q000235:genetics*
D017931:DNA Primers; D012333:RNA, Messenger; D014758:Viral Core Proteins