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

Author

Listed:
  • Joshua A. Hill

    (University of Washington
    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
    Clinical Research Division, Fred Hutchinson Cancer Center)

  • Yeon Joo Lee

    (Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • 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
    Seattle Children’s Hospital)

  • Guang-Shing Cheng

    (University of Washington
    Clinical Research Division, Fred Hutchinson Cancer Center)

  • Haiying Zhu

    (University of Washington)

  • Meei-Li Huang

    (University of Washington)

  • Geoffrey R. Hill

    (Clinical Research Division, Fred Hutchinson Cancer Center
    Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center)

  • Keith R. Jerome

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
    University of Washington)

  • Wendy M. Leisenring

    (Clinical Research Division, Fred Hutchinson Cancer Center)

  • Danielle M. Zerr

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
    Seattle Children’s Hospital)

  • Sina A. Gharib

    (University of Washington)

  • Sanjeet Dadwal

    (City of Hope National Medical Center)

  • Michael Boeckh

    (University of Washington
    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
    Clinical Research Division, Fred Hutchinson Cancer Center)

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.

Suggested Citation

  • 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. Leisenr, 2024. "HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44828-9
    DOI: 10.1038/s41467-024-44828-9
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