Cytomegalovirus Spread and Reactivation in Blood Cells

BACKGROUND:

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. 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.

DESIGN NARRATIVE:

The specific aims of the study were to: 1) examine the percentage of HCMV positive donors whose bone marrow progenitors contained HCMV DNA using nested PCR and determine if virus could be rescued from those cells. 2) Analyze the HCMV life cycle in hematopoietic progenitor and stem cells. 3) identify and analyze HCMV gene expression in in vivo infected leukocytes. Bone marrow progenitors containing HCMV DNA detectable by nested PCR were 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 were important in either establishing or maintaining a latent infection or in the lytic cycle of HCMV. Information provided from the above studies yielded information important in planning future approaches for the therapy of HCMV infections.