HUMAN CYTOMEGALOVIRUS-INFECTION OF THE MONOCYTE MACROPHAGE LINEAGE INBONE-MARROW/

Peripheral blood monocytes (PBM) are one site of persistence of human cytomegalovirus (HCMV) in healthy carriers. However, because PBM circu late only briefly before entering the tissues and are difficult to inf ect with HCMV, it has been suggested that they may acquire HCMV during development in the bone marrow. Consistent with this, we show evidenc e that bone marrow progenitors from healthy HCMV carriers contain endo genous HCMV DNA as detected by PCR. We also show that bone marrow prec ursors are readily infected by clinical isolates of HCMV in vitro but that no viral gene expression occurs until these cells become differen tiated. In contrast, incubation of these cells at any developmental st age with the laboratory strain AD169 resulted in few cells expressing viral immediate-early genes, and this correlated with a lack of entry of AD169 virus. These observations are consistent with bone marrow pro genitors acting as reservoir for HCMV and transmitting the viral genom e to PBM, in the absence of lytic-gene expression, until they leave th e circulation and undergo tissue-specific differentiation to macrophag es.