Endothelial cells (EC) have been discussed as candidates. In HCT with either donor or recipient or both being latently infected, hCMV can reactivate from latently infected donor cells of the myeloid hematopoietic lineage, as well as from latently infected cells present in the transplant recipient, presumably including a tissue cell type that is refractory to hematoablative antitumor therapy. On top of this, in the case of allogeneic HCT with family or unrelated donors differing in major (HLA) and/or minor histocompatibility antigens (mHAg), additional immunosuppressive therapy is applied to prevent graft-versus-host (GvH) disease (for clinical overviews, see ).

Patients at risk of CMV disease following productive reactivation of latent virus are recipients of solid-organ transplantation (SOT), who become immunosuppressed to prevent graft rejection, as well as recipients of hematopoietic cell transplantation (HCT) transiently immunocompromised by hematoablative therapy of aggressive hematopoietic malignancies that are refractory to standard antitumoral therapies. However, there is increasing evidence for viral gene expression during latency that does not follow the canonical temporal cascade of gene expression during productive infection and that can impact the cellular secretome to create a latency-modulated microenvironment. Īfter clearance of productive CMV infection, a latent infection, briefly referred to as “latency”, is established, which is defined by the presence of replication-competent viral genomes that are silenced at loci critical for completion of the viral replicative cycle so that infectious progeny is not produced. Ī significant public health and economic impact, and the main argument for the development of a CMV vaccine, results from birth defects caused by hCMV in an immunologically immature embryo/fetus after congenital infection following diaplacental transmission of the virus after primary or recurrent infection during pregnancy.

Whereas primary infection passes mostly undiagnosed without overt clinical symptoms or organ disease when held in check by an intact innate and adaptive immune system in the otherwise healthy, immunocompetent host, unrestricted cytopathogenic tissue infection can lead to multiple-organ failure with often lethal outcome in an immunocompromised host. Human cytomegalovirus (hCMV) is a prototype member of the β-subfamily of the herpes virus family.

Evc prototype 1