Despite progress in understanding the pathophysiology of human cytomegalovirus (HCMV) infections, its manifestations in the immune compromised host are frequently associated with high morbidity and mortality. In this setting, HCMV disease can develop e.g. following immune suppression as a result of reactivation of latent HCMV acquired earlier in life (1;2). The mechanisms leading to establishment of latent infections and their subsequent reactivation are not clear. It is also unknown whether HCMV exists in a latent form with limited viral gene expression or as a persistent infection with normal virus transcription. We propose to investigate the relationship between HCMV and bone marrow progenitor cells to understand whether HCMV is latent in CD34 + bone marrow progenitors and the mechanism by which the virus remains in a latent state. This overall goal will be pursued as follows. 1) Determine the percentage of HCMV positive donors whose bone marrow progenitors contain HCMV DNA using nested PCR and determine if virus can be rescued from those cells. 2) Analysis of the HCMV life cycle in hematopoietic progenitor and stem cells. 3) Identification and analysis of HCMV gene expression in in vivo infected leukocytes. Bone marrow progenitors containing HCMV DNA detectable by nested PCR will be isolated from human donors and used as as source of mRNA to prepare Cdna libraries. 4) Determine if gene(s) expressed in bone marrow progenitors are important in either establishing or maintaining a latent infection or in the lytic cycle of HCMV. Information provided from the above studies will yield information that will be important in planning future approaches for the therapy of HCMV infections.
