Inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) is present in approximately 1% of the population, but its clinical significance remains uncertain. This study describes a pediatric hematopoietic stem cell transplant (HSCT) recipient with maternally inherited HHV-6A who developed severe systemic complications and markedly delayed immune reconstitution following transplantation.
Although neutrophil engraftment and full donor chimerism were achieved, the patient experienced persistent cytopenia, irritability, renal dysfunction, hyponatremia, pulmonary and pericardial edema, and impending cardiac tamponade. HHV-6A DNA remained elevated in blood and was also detected in cerebrospinal and pericardial fluids, while testing for other common post-transplant viral infections was negative. Profound T-cell lymphopenia and poor graft function persisted during the first months following HSCT.
The patient received a CD34+ stem-cell booster followed by four weeks of ganciclovir treatment. This was associated with a substantial decline in HHV-6A DNA levels, rapid resolution of systemic symptoms, improved hematopoietic function, and progressive immune reconstitution.
Complementary molecular analyses provided evidence of active HHV-6A replication. Viral DNA became predominantly unmethylated after transplantation, encapsidated viral DNA was detected in pericardial fluid following DNase treatment, and targeted sequencing demonstrated the emergence of several minor viral variants that were absent before HSCT. Viral diversity subsequently contracted following treatment.
These findings indicate that recipient-derived iciHHV-6A can reactivate after HSCT and may contribute to clinically significant disease, impaired graft function, and delayed immune recovery. The study also demonstrates that viral DNA demethylation, DNase protection assays, and longitudinal minor-variant analysis can support the identification of iciHHV-6 reactivation when suitable samples for viral RNA or protein detection are unavailable.
Original article:
Leo Hannolainen, Heljä Lång, Lari Pyöriä, et al. Inherited HHV-6A reactivation linked to impaired immune reconstitution following hematopoietic stem cell transplantation. Haematologica. 2026 Apr 16. doi: 10.3324/haematol.2026.300575.