Since scientists first observed the phenomenon of chromosomal integration of HHV-6 (ciHHV-6), it has been unclear whether individuals with this condition could experience reactivation of the virus with pathogenic effects on the human body. Now, for the first time, a group in Japan has presented convincing molecular and virological evidence that a patient’s integrated strain can activate to produce infectious virions. The activated integrated strain triggered hemophagocytic syndrome (HPS), which was treated successfully with antivirals.

Earlier reports on ciHHV-6 suggested that it was unlikely that the integrated virus could activate and that all patients determined to have ciHHV-6 should have their antiviral medications withdrawn. These assumptions have now been proven wrong on both counts, and the new findings have significant implications for the management of patients with ciHHV-6 moving forward. In an accompanying editorial, ciHHV6 expert Louis Flamand has called for transplant centers to initiate ciHHV-6 screening programs.  READ MORE

A team of HHV-6 investigators led by Wayne State University Professor Phil Pellett, PhD, organized a one-day Roseolovirus Workshop at the NIH on June 2nd. The purpose of the meeting was to raise awareness and identify high priority research questions and critical unmet needs. Over 50 researchers and clinicians attended the workshop organized by Pellett and Co-Chair Mary Caserta, MD from University of Rochester. The workshop was funded with a grant from the NIAID, and support from the HHV-6 Foundation.  READ MORE

In a recent study published in the European Journal of Allergy and Clinical Immunology, a group from Kyorin University School of Medicine in Tokyo sought to comprehensively record the dynamics of key herpesviruses beyond the acute stage of SJS/TEN.  The group found persistently increased EBV loads in SJS during the acute stage and long after resolution, but not in others. Conversely, high HHV-6 loads were exclusively detected in DIHS/DRESS during the acute stage.  The dynamics of herpesvirus reactivation also varied in DIHS/DRESS according to the use of systemic corticosteroids: While EBV loads were higher in patients not receiving systemic corticosteroids, CMV and HHV-6 loads were higher in those receiving them.  READ MORE

A group of investigators in Japan have determined that an inflammatory cytokine released in response to trauma, stress, and surgery is highly elevated in DIHS/DRESS patients compared to those with other forms of severe cutaneous adverse drug reactions (cADR) such as Stevens-Johnson Syndrome (SJS) or toxic epidermal necrosis (TEN). High mobility group box 1 protein (HMGB-1) is a nuclear protein that is produced by severely damaged cells and serves as a pro-inflammatory cytokine once released from the cell.  READ MORE

A group from Tokyo Medical University has determined that low level HHV-6 reactivation, but not CMV, EBV or HHV-7 reactivation, is a predictive marker for the development of grade 2-4 acute GVHD after hematopoietic stem cell transplantation (HSCT).  To determine correlations between viral reactivation and transplantation-related complications, 49 patients who underwent HSCT were subjected to various viral screening tests on the 30th day after allogeneic hematopoietic stem cell transplantation (HSCT), and monitored for clinical implications in the days following.  Reactivation of CMV, EBV, HHV-6, and HHV-7 was detected in 44.9%, 22.4%, 53.1%, and 18.3% of patients, respectively.  However, when these reactivation events were subsequently compared with clinical complications, a significant correlation was found only between HHV-6 and grade 2-4 aGVHD from day 30 to day 100.

Furthermore, multivariate analysis revealed that a cutoff value of 87 copies/mL was sufficient as a threshold for HHV-6 positivity related to cumulative incidence of grade 2-4 acute GVHS on or after post-HSCT day 30.  This study is consistent with several previous reports suggest that HHV-6 reactivation plays a role in causing severe GVHD and the delay of thrombocyte engraftment, resulting in poor outcomes. READ MORE