Pascale Bonnafous1, Tuan L Phan2,3, Ryan Himes4, Karen Eldin4, Agnès Gautheret-Dejean5,6, Bhupesh K Prusty7, Henri Agut5, Flor M Munoz4. 1. Sorbonne Department, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP), THERAVIR team, Paris, France. 2. Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana. 3. HHV-6 Foundation, Santa Barbara, California. 4. Departments of Pediatrics, Molecular Virology and Microbiology, Hepatology, and Pathology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas. 5. AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Service de Virologie, Paris, France. 6. Department Paris Descartes, Institute de Pharmacie de Paris, UMR-S 1139 (3PHM), Paris, France. 7. Institute for Virology and Immunobiology, Wuerzburg, Germany.
Abstract
BACKGROUND: Active infections of human herpesvirus 6B (HHV-6B) are frequent in immunocompromised recipients after transplantation. Nevertheless, they need to be distinguished from latent inherited chromosomally integrated genomes (iciHHV-6) present in about 1% of the population to avoid unnecessary administration of toxic antivirals. METHODS: A 5-year-old child presented with acute liver allograft rejection associated with HHV-6 DNA in plasma, which led to an unfavorable outcome. We investigated the possibility of HHV-6 infection derived from an iciHHV-6 present in the donor's liver using molecular and histopathology studies in various tissues, including quantification of HHV-6 DNA, genotyping, sequencing for antiviral resistance genes, relative quantification of viral transcripts, and detection of gB and gH viral proteins. RESULTS: The presence of iciHHV-6B was evidenced in the donor with signs of reactivation in the gallbladder and transplanted liver (detection of HHV-6B mRNA and late proteins). This localized expression could have played a role in liver rejection. Low viral loads in the recipient's plasma, with identical partial U39 sequences, were in favor of viral DNA released from the transplanted liver rather than a systemic infection. CONCLUSIONS: Determination of iciHHV-6 status before transplantation should be considered to guide clinical decisions, such as antiviral prophylaxis, viral load monitoring, and antiviral therapy.
BACKGROUND: Active infections of human herpesvirus 6B (HHV-6B) are frequent in immunocompromised recipients after transplantation. Nevertheless, they need to be distinguished from latent inherited chromosomally integrated genomes (iciHHV-6) present in about 1% of the population to avoid unnecessary administration of toxic antivirals. METHODS: A 5-year-old child presented with acute liver allograft rejection associated with HHV-6 DNA in plasma, which led to an unfavorable outcome. We investigated the possibility of HHV-6 infection derived from an iciHHV-6 present in the donor's liver using molecular and histopathology studies in various tissues, including quantification of HHV-6 DNA, genotyping, sequencing for antiviral resistance genes, relative quantification of viral transcripts, and detection of gB and gH viral proteins. RESULTS: The presence of iciHHV-6B was evidenced in the donor with signs of reactivation in the gallbladder and transplanted liver (detection of HHV-6B mRNA and late proteins). This localized expression could have played a role in liver rejection. Low viral loads in the recipient's plasma, with identical partial U39 sequences, were in favor of viral DNA released from the transplanted liver rather than a systemic infection. CONCLUSIONS: Determination of iciHHV-6 status before transplantation should be considered to guide clinical decisions, such as antiviral prophylaxis, viral load monitoring, and antiviral therapy.
Authors: Michael L Wood; Colin D Veal; Rita Neumann; Nicolás M Suárez; Jenna Nichols; Andrei J Parker; Diana Martin; Simon Pr Romaine; Veryan Codd; Nilesh J Samani; Adriaan A Voors; Maciej Tomaszewski; Louis Flamand; Andrew J Davison; Nicola J Royle Journal: Elife Date: 2021-09-21 Impact factor: 8.140
Authors: Krupa R Mysore; Tuan L Phan; Ryan W Himes; Deborah Schady; Karen W Eldin; Bhupesh K Prusty; Flor M Munoz Journal: J Pediatric Infect Dis Soc Date: 2021-05-28 Impact factor: 3.164