HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant
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 allo...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-44828-9 |
| _version_ | 1827377246401200128 |
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| author | 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 Michael Boeckh |
| author_facet | 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 Michael Boeckh |
| author_sort | Joshua A. Hill |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T12:36:16Z |
| format | Article |
| id | doaj.art-39b047bf5fcd49bdbe59380335b671b1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T12:36:16Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-39b047bf5fcd49bdbe59380335b671b12024-01-21T12:26:37ZengNature PortfolioNature Communications2041-17232024-01-0115111210.1038/s41467-024-44828-9HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplantJoshua A. Hill0Yeon Joo Lee1Lisa K. Vande Vusse2Hu Xie3E. Lisa Chung4Alpana Waghmare5Guang-Shing Cheng6Haiying Zhu7Meei-Li Huang8Geoffrey R. Hill9Keith R. Jerome10Wendy M. Leisenring11Danielle M. Zerr12Sina A. Gharib13Sanjeet Dadwal14Michael Boeckh15Department of Medicine, University of WashingtonInfectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, University of WashingtonClinical Research Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterDepartment of Medicine, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonClinical Research Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterClinical Research Division, Fred Hutchinson Cancer CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer CenterDepartment of Medicine, University of WashingtonCity of Hope National Medical CenterDepartment of Medicine, University of WashingtonAbstract 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.https://doi.org/10.1038/s41467-024-44828-9 |
| spellingShingle | 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 Michael Boeckh HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant Nature Communications |
| title | HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant |
| title_full | HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant |
| title_fullStr | HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant |
| title_full_unstemmed | HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant |
| title_short | HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant |
| title_sort | hhv 6b detection and host gene expression implicate hhv 6b as pulmonary pathogen after hematopoietic cell transplant |
| url | https://doi.org/10.1038/s41467-024-44828-9 |
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