HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant

Joshua A. Hill (), Yeon Joo Lee, Lisa K. Vande Vusse, Hu Xie, E. Lisa Chung, Alpana Waghmare, Guang-Shing Cheng, Haiying Zhu, Meei-Li Huang, Geoffrey R. Hill, Keith R. Jerome, Wendy M. Leisenring, Danielle M. Zerr, Sina A. Gharib, Sanjeet Dadwal and Michael Boeckh
Additional contact information
Joshua A. Hill: University of Washington
Yeon Joo Lee: Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center
Lisa K. Vande Vusse: University of Washington
Hu Xie: Clinical Research Division, Fred Hutchinson Cancer Center
E. Lisa Chung: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Alpana Waghmare: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Guang-Shing Cheng: University of Washington
Haiying Zhu: University of Washington
Meei-Li Huang: University of Washington
Geoffrey R. Hill: Clinical Research Division, Fred Hutchinson Cancer Center
Keith R. Jerome: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Wendy M. Leisenring: Clinical Research Division, Fred Hutchinson Cancer Center
Danielle M. Zerr: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
Sina A. Gharib: University of Washington
Sanjeet Dadwal: City of Hope National Medical Center
Michael Boeckh: University of Washington

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Limited understanding of the immunopathogenesis of human herpesvirus 6B (HHV-6B) has prevented its acceptance as a pulmonary pathogen after hematopoietic cell transplant (HCT). In this prospective multicenter study of patients undergoing bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT, we test blood and BAL fluid (BALF) for HHV-6B DNA and mRNA transcripts associated with lytic infection and perform RNA-seq on paired blood. Among 116 participants, HHV-6B DNA is detected in 37% of BALs, 49% of which also have HHV-6B mRNA detection. We establish HHV-6B DNA viral load thresholds in BALF that are highly predictive of HHV-6B mRNA detection and associated with increased risk for overall mortality and death from respiratory failure. Participants with HHV-6B DNA in BALF exhibit distinct host gene expression signatures, notable for enriched interferon signaling pathways in participants clinically diagnosed with idiopathic pneumonia. These data implicate HHV-6B as a pulmonary pathogen after allogeneic HCT.

Date: 2024
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DOI: 10.1038/s41467-024-44828-9

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