Human cytomegalovirus induced inhibition of hematopoietic cell line growth is initiated by events taking place before translation of viral gene products

Bone marrow suppression with leukopenia is frequently observed during human cytomegalovirus (HCMV) infection, and in vitro the cell colony formation of bone marrow progenitors is directly inhibited by HCMV. To better understand the mechanisms of HCMV's ability to directly inhibit the cell colony formation of hematopoietic cells, we examined the effect of HCMV infection on four hematopoietic cell lines, ML-3, HL-60, KG-1, and U-937. Similarly to the observed effect on hematopoietic progenitors, HCMV significantly inhibited the cell colony formation of KG-1 and U-937 cells, 40% and 30% respectively. Following HCMV infection, uptake of HCMV pp65 was detected in all cell lines. In contrast, no immediate early protein production could be observed. When the cell line KG-1 was challenged with UV-inactivated HCMV or with HCMV dense bodies, containing pp65 and other matrix proteins, a 20% to 25% inhibition of cell colony formation was found. In addition, a dose-dependent inhibition of proliferation of the KG-1 cells challenged with intact or UV-inactivated HCMV, was observed. Transfection of this cell line with vectors containing genes for the HCMV matrix protein pp65, revealed no inhibitory effect. In contrast, the transfection with pp71 resulted in a 20% growth inhibition. These results indicate that HCMV can induce inhibition of cell colony formation of hematopoietic cells without transcription of HCMV regulatory proteins, and that at least one HCMV matrix protein may play an important role in this inhibitory effect.