Measles virus nucleocapsid transcript expression is not restricted to the osteoclast lineage in patients with Paget's disease of bone

Abundant evidence supports a viral etiology for Paget's disease of bone (PD ), however, an infectious virus has not been isolated from PD patients. Thu s, it is unclear how the virus is maintained for the many years that the di sease persists in patients, We considered if a primitive multipotential hem atopoietic stem cell (HSC), which is self-renewing, passes the virus to its differentiated progeny and serves as a reservoir for the pathogen, If a pr imitive stem cell harbored measles virus (MV), then other hematopoietic lin eages derived from this stem cell in PD patients should also express MV tra nscripts. Therefore, because the human hematopoietic stem cell has not been clearly identified or isolated in large numbers, we isolated RNA from high ly purified erythroid and multipotential hematopoietic progenitors that are the precursors for erythroid, granulocyte, megakaryocyte and macrophages ( CFU-GEMM), and used RT-PCR to deter-mine if MV nucleocapsid transcripts wer e present. MV transcripts were detected in PD patients in early erythroid ( BFU-E) and more primitive multipotential myeloid progenitors (CFU-GEMM), No nhematopoietic stromal cells from PD patients did not ex-press MV transcrip ts. The expression of MV transcripts in erythroid progenitors was further c onfirmed by in situ hybridization using antisense riboprobes to MV nucleoca psid transcripts. Thus, our findings suggest that the pluripotent HSCs may be a potential reservoir for the virus. We propose that when HSCs, which co ntain MV, divide they produce a second HSC that serves as a reservoir for t he virus and also transmit the virus to their more differentiated progeny i n the erythroid and myeloid lineages. This mechanism would permit a defecti ve virus to persist in HSCs of PD patients for many Sears, since HSCs are u sually in GU phase, and then be transmitted to more differentiated cells. T his model further suggests that a mature complete virus that affects cell f unction could only act pathogenetically in the osteoclast lineage, which of fers a permissive milieu. (C) 1999 International Society for Experimental H ematology. Published by Elsevier Science Inc.