HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant Journal Article
| Authors: | Hill, J. A.; Lee, Y. J.; Vande Vusse, L. K.; Xie, H.; Chung, E. L.; Waghmare, A.; Cheng, G. S.; Zhu, H.; Huang, M. L.; Hill, G. R.; Jerome, K. R.; Leisenring, W. M.; Zerr, D. M.; Gharib, S. A.; Dadwal, S.; Boeckh, M. |
| Article Title: | 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 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. © 2024, The Author(s). |
| Keywords: | adult; clinical article; genetics; prednisone; clinical feature; clinical trial; mortality; alpha interferon; comparative study; cytarabine; prospective study; prospective studies; reverse transcription polymerase chain reaction; apoptosis; gene expression; bone marrow; etoposide; genome-wide association study; notch receptor; melphalan; hematopoietic stem cell transplantation; genetic transcription; carmustine; coughing; dyspnea; pneumonia; extracellular matrix; blood; myeloablative conditioning; dna; messenger rna; rna, messenger; multicenter study; allogeneic hematopoietic stem cell transplantation; umbilical cord blood; dna fingerprinting; fc receptor; cidofovir; real time polymerase chain reaction; upregulation; oxidative stress; virus load; leukocyte count; graft rejection; virus replication; corticosteroid; bordetella pertussis; transcriptome; beta interferon; umbilicus; oxidative phosphorylation; foscarnet; ganciclovir; adenovirus infection; cytomegalovirus infection; integrin; rho guanine nucleotide binding protein; cell organelle; oxygen saturation; hla antigen; aspergillus; graft recipient; genomic dna; virus pneumonia; predictive value; virus detection; oxygen supply; receiver operating characteristic; host; respiratory failure; antiviral therapy; lung lavage; cumulative incidence; virus dna; angiopoietin; complication; idiopathic disease; viremia; limit of detection; virus pathogenesis; false discovery rate; pathogen; amino acid metabolism; pneumocystis jiroveci; lung mycosis; notch signaling; absolute lymphocyte count; limit of quantitation; humans; human; male; female; article; human herpesvirus 6; rna sequencing; exanthema subitum; differential gene expression; absolute neutrophil count; lower respiratory tract; multidimensional scaling; herpesvirus 6, human; mycoplasma pneumoniae; gene set enrichment analysis; comorbidity assessment; matched related donor; matched unrelated donor; real time reverse transcription polymerase chain reaction; whole transcriptome sequencing; interferon signaling; human herpesvirus 6b; roseolovirus infections; chlamydia pneumoniae |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-01-16 |
| Start Page: | 542 |
| Language: | English |
| DOI: | 10.1038/s41467-024-44828-9 |
| PUBMED: | 38228644 |
| PROVIDER: | scopus |
| PMCID: | PMC10791683 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
