Deciphering Cytomegalovirus Reactivation in Viremic Patients

Human cytomegalovirus (HCMV) infects over half of adults by age 40. The infection is mostly asymptomatic; however, it is followed by a lifelong latent infection. HCMV reactivation following hematopoietic stem cell transplantation (HSCT) is a major cause of patient mortality. Due to the high risk HCMV reactivation poses in these patients, they are weekly monitored for virus levels in the blood. The specific cell type in which HCMV reactivation occurs is unknown, and it is unclear which cells carry the virus in the blood during viremia.

To elucidate the sub-population of blood cells infected by HCMV we utilized an experimental system of HCMV infection ex-vivo. Infection of peripheral blood mononuclear cells (PBMC) harvested from healthy donors resulted in prominent infection of CD14+ monocytes, while CD14- cells were infected to a lower level. Further, we analyzed PBMC harvested from patients that received HSCT and were diagnosed with HCMV reactivation. PBMC from viremic samples were divided to sub-populations and analysed to determine viral DNA levels. Surprisingly, in this physiological setting, CD14+ monocytes were not the main cell carrying HCMV DNA. We are focusing on characterizing the cell population which is infected among PBMC in these patients. Finding these cells will help elucidate the progression of HCMV infection and will allow us to enrich for this cell population in order to study viral and host gene expression during HCMV infection in a physiologically relevant setting. Overall, studying host-virus interactions during HCMV viremia may bring forward potential therapeutic strategies for treatment of immunosuppressed patients.