Roseoloviruses in transplant recipients: clinical consequences and prospects for treatment and prevention trials

Abstract

Roseoloviruses frequently reactivate in transplant recipients. We review the impact of Roseoloviruses in transplant recipients and highlight research priorities. Human herpesvirus 6A (HHV-6A) and HHV-6B were recently classified as distinct species with important differences. Both viruses can result in inherited chromosomally integrated HHV-6, which may cause complications after transplant. HHV-6B is the primary species associated with disease and appears to have pleiotropic effects on the central nervous system. Small preemptive and prophylactic studies have not shown a statistically significant impact on HHV-6 disease. Although Roseoloviruses are associated with diverse complications in transplant patients, studies providing strong evidence for a causal role are lacking. Trials focusing on prevention and treatment will be important to inform the significance of Roseolovirus reactivation.

Stabilization of Telomere G-Quadruplexes Interferes with Human Herpesvirus 6A Chromosomal Integration

“…1). Binding of 1H6 antibodies to G-rich oligonucleotides [(TTAGGG) 4 ] was also observed. Marginal binding to the singlestranded DNA (ssDNA) was recorded, as previously reported (41,42).…”

“…To ensure the correct folding of oligonucleotides into G-quadruplex structures, we initially performed an enzyme-linked immunosorbent assay (ELISA) using the BG4 and 1H6 antibodies that specifically bind to G-quadruplex structures. We demonstrated that the BG4 antibodies preferentially bind G-rich oligonucleotides, such as the telomeric [(TTAGGG) 4 ] and myc oligonucleotides. The latter corresponds to a DNA sequence present in the promoter of the MYC gene and was previously reported to fold into a G-quadruplex structure (38)(39)(40) (Fig.…”

“…It is the etiological agent of the febrile illness roseola infantum, also known as the sixth childhood eruptive disease (2,3). Reactivation of HHV-6B in immunosuppressed individuals is associated with adverse clinical outcomes, including life-threatening encephalitis or graft rejection in transplant patients (4). The diseases associated with HHV-6A infection are not clearly established.…”

Outcomes of hematopoietic cell transplantation using donors or recipients with inherited chromosomally integrated HHV-6

“…1,2 HHV-6B reactivation based on DNA detection in serum or plasma occurs in 30% to 50% of allogeneic hematopoietic cell transplant (HCT) recipients, is the most frequent cause of infectious encephalitis, and is associated with acute graft-versus-host disease (GVHD), cytopenias, cytomegalovirus (CMV) reactivation, and increased overall mortality. 3 The epidemiology and clinical consequences of HHV-6A are less well understood.…”

Detection of Human Herpesvirus 6B (HHV-6B) Reactivation in Hematopoietic Cell Transplant Recipients with Inherited Chromosomally Integrated HHV-6A by Droplet Digital PCR

“…This has been associated with complications, such as central nervous system dysfunction, fever and rash, myelosuppression, graft rejection, and acute graft-versus-host disease (GVHD), some of which have also been reported after solid organ transplantation (8). While further research is needed to determine the clinical significance of inherited ciHHV-6A or -B after transplantation, it is well recognized that inherited ciHHV-6A or -B complicates molecular diagnostic testing for HHV-6B reactivation (9,10).…”