Persistence of cytomegalovirus in human long-term bone marrow culture: relationship to hemopoiesis

Abstract

Using pre-established human long-term marrow culture (LTMC), we studied cytomegalovirus (CMV) replication in this system after in vitro infection of nonadherent cells obtained from these cultures with CMV AD-169. After infection with 5 immediate-early antigen foci/cell CMV was detectable for 63-123 days (peak titer 2.0 x 10(3)-1.3 x 10(9)) in the supernatants of LTMC. Lower MOI resulted in a delay in the detection and longer persistence of CMV in LTMC although peak titers were unchanged. CMV infection was associated with destruction of the stromal layer, appearance of a subset of large (23 microns) CMV-infected mononuclear cells in the nonadherent fraction, and early differentiation of nonadherent cells into a homogenous population of macrophage-like cells. CMV infection resulted in a reduction and premature disappearance of committed progenitors (BFU-E, CFU-GM) in LTMC. Persistence of CMV in LTMC was linked to ongoing hemopoiesis. Human bone marrow may be an important site for CMV replication during acute infection and CMV persistence.