Human cytomegalovirus infection of human hematopoietic progenitor cells

For a number of years it has been well established that human cytomegalovirus (HCMV) can be transmitted by the cellular components of blood. HCMV is also associated with a number of hematologic disorders. Although HCMV was thought to be present in blood cells in a latent or persistent form, it was not known how the virus was maintained and which cells were the carriers of HCMV. In addition to peripheral blood cells, there has been clinical evidence that HCMV may be associated with specific disorders of the hematopoietic system. Recently, a number of advances in cell and molecular biology have helped to develop a better understanding of the relationship between HCMV and the hematopoietic system. The application of the polymerase chain reaction (PCR) to the study of HCMV infection has revealed that the virus was present in mononuclear cells with only limited transcription of its genome. Studies conducted in our laboratory have demonstrated that both CD34+ progenitor cells and monocytes could be infected with HCMV and virus recovered when the cells were allowed to terminally differentiate. Subsequently, these results have been confirmed in vivo: HCMV DNA and limited RNA transcripts could be detected in in vivo infected hematopoietic progenitor cells and HCMV has been rescued from macrophages derived through in vitro differentiation of monocytes from normal seropositive blood donors. Although our understanding of the relationship between HCMV and the hematopoietic system has been advanced, the mechanisms by which the virus can be maintained in a latent state and how it is reactivated is still unclear. Furthermore, it remains to be determined what HCMV-mediated effect is responsible for the inhibition of hematopoiesis following an in vitro infection and its significance in vivo.