Chromosomally integrated human herpesvirus‐6 in transplant recipients

Abstract

Human herpesvirus-6 (HHV-6) is unique among human herpesviruses because of its ability to integrate into chromosomes. This entity, termed chromosomally integrated HHV-6 (CIHHV-6), is often mistaken for active infection and treated unnecessarily. The clinical significance of CIHHV-6 in transplant recipients is not defined. Herein, the clinical characteristics of 7 liver transplant patients with CIHHV-6 from our recent study, together with 14 other published cases of CIHHV-6 were reviewed. Of the 21 cases, CIHHV-6B was reported most commonly among solid organ transplant recipients, while CIHHV-6A was mostly seen in allogeneic hematopoietic stem cell recipients. None of the 21 patients developed clinical symptoms related to HHV-6 after transplantation. However, antiviral therapy was administered to 5 asymptomatic patients mistaken to have HHV-6 infection because of their very high HHV-6 DNA levels, 3 who developed symptomatic cytomegalovirus disease, and 1 with graft-versus-host disease that was mistaken for HHV-6 infection. In patients who received antiviral therapy, there was no apparent decline in HHV-6 DNA load, although change in viral kinetics is difficult to discern in the setting of high baseline HHV-6 DNA load. Clinicians should be aware of this entity of CIHHV-6 so that antiviral therapy can be considered in the proper clinical context.

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

“…32 Individuals with ciHHV-6 always show abnormally high copy numbers of HHV-6 DNA in whole blood, and cerebrospinal PCR testing for HHV-6 may also become positive in patients with cerebrospinal fluid pleocytosis. 27,33 As described below, blood HHV-6 DNA levels usually appear high in patients with HHV-6 encephalitis and the demonstration of positive HHV-6 DNA in cerebrospinal fluid is an important condition for diagnosis. As a result, ciHHV-6 should be carefully excluded before HHV-6 encephalitis is diagnosed.…”

Emerging Technologies for the Clinical Microbiology Laboratory

“…Differentiation is based on accurate determination of the ratio of HHV-6 to a eukaryotic cell marker, which is less precise using standard qPCR. This distinction is critical for posttransplant patients with a high HHV-6 load, since ciHHV-6 is often not associated with disease (126). Despite the current paucity of clinical studies, based on these examples it is easy to speculate that the primary strength of dPCR in infectious disease is quantification of viral load, including identification of minor species in a specimen, such as drug-resistant HIV quasispecies.…”

“…Disease progression, prognosis, selection of antivirals, and response to therapy have been linked to the initial viral load or changes in load observed during continuous monitoring for HIV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and BK virus (121)(122)(123)(124)(125)(126). Likewise, identification and quantification of genetic markers of malignancy, including mutations, rearrangements, and expression of dysfunctional microRNAs (miRNAs), can aid in management of these patients (127)(128)(129)(130).…”

Is Isolation of Human Herpesvirus 6 in Kidney Transplant Recipients Clinically Significant?

“…HHV-6 specific antigens have been detected by immunohistochemistry in kidney biopsies of patients with acute and chronic rejection or cyclosporine-related nephropathy while high viral loads in renal tissue have been correlated with significant illness owing to HHV-6 infection of pediatric kidney transplant patients [1,5,7]. Nucleic acid testing has also allowed for detection of chromosomally integrated HHV-6 (CIHHV-6) in kidney transplant recipients [8]. However the significance of the persistent HHV-6 regarding transplant outcome remains uncertain [8].…”

“…Nucleic acid testing has also allowed for detection of chromosomally integrated HHV-6 (CIHHV-6) in kidney transplant recipients [8]. However the significance of the persistent HHV-6 regarding transplant outcome remains uncertain [8].…”