In vitro infection of megakaryocytes and their precursors by human cytomegalovirus

Apart from congenital human cytomegalovirus(HCMV) infection, manifest HCMV disease occurs primarily in immunocompromised patients. In allogeneic bone marrow transplantation, HCMV is frequently associated with graft failure an d cytopenias involving all hematopoietic lineages, but thrombocytopenia is the most commonly reported hematologic complication. The authors hypothesiz ed that megakaryocytes (MK) may be a specific target for HCMV, Although the susceptibility of immature hematopoietic progenitors cells to HCMV has bee n established, a productive viral life cycle has only been linked to myelom onocytic maturation. The authors investigated whether HCMV can also infect MK and impair their function. They demonstrated that HCMV did not affect th e thrombopoietin (TPO)-driven proliferation of CD34(+) cells until MK matur ation occurred. MK challenged with HCMV showed a 50% more rapid loss of via bility than mock-infected cells. MK and their early precursors were clearly shown to be susceptible to HCMV in vitro, as evidenced by the presence of HCMV in magnetic column-purified CD42(+) MK and P-color fluorescent stainin g with antibodies directed against CD42a and HCMV pp65 antigen, These findi ngs were confirmed by the infection of MK with a laboratory strain of HCMV containing the beta-galactosidase (beta-gal) gene. Using chromogenic beta-g al substrates, HCMV was detected during MK differentiation of infected CD34 (+) cells and after infection of fully differentiated MK, Production of inf ectious virus was observed in cultures infected MK, suggesting that HCMV ca n complete its life cycle. These results demonstrate that MK are susceptibl e to HCMV infection and that direct infection of these cells in vivo may co ntribute to the thrombocytopenia observed in patients infected with HCMV. ( Blood. 2000;95:487-493) (C) 2000 by The American Society of Hematology.