SPREAD OF HUMAN CYTOMEGALOVIRUS (HCMV) AFTER INFECTION OF HUMAN HEMATOPOIETIC PROGENITOR CELLS - MODEL OF HCMV LATENCY

Clinical experience and laboratory data suggest that human cytomegalov irus (HCMV) is present in peripheral blood of seropositive individuals in a latent or persistent state and can be transmitted via blood prod ucts and be reactivated in seropositive imunocompromised patients. The pathophysiology of HCMV latency and the nature of HCMV interaction wi th hematopoietic cells remains unknown, In this study, we investigated the infection of bone marrow (BM) progenitor cells and their progeny as a model of HCMV latency. A clinical isolate and the recombinant lab oratory strain Towne/lox containing the Escherichia coli beta galactos idase (beta-gal) gene regulated by immediately early (IE) HCMV promote r were used to infect highly purified CD34(+) cells. Although the infe ction of these cells with a clinical isolate was associated with an in hibition of proliferation by 59%, an expansion of progeny derived from these cells was possible. Polymerase chain reaction analysis and stai ning for beta-gal have shown that HCMV persisted in infected BM CD34() cells and their progeny for up to 4 weeks. However, IE and late gene products (mRNA and protein) were detected only late in the course of infection and their expression correlated with terminal macrophage dif ferentiation of the CD34(+)-derived progeny. Although early infection of CD34(+) progenitor cells was not productive (as shown by the plaque assay), infectious virus could be recovered from the terminally diffe rentiated cultures. BM progenitor cells may serve as a reservoir of th e latent virus with limited transcription, Proliferation and monocytic maturation of infected progenitors may lead to the numerical expansio n of HCMV-infected cells, which serve as a source of HCMV disseminatio n and reactivation. (C) 1997 by The American Society of Hematology.