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

Area of Science:

• Virology
• Immunology
• Pulmonology
• Hematology

Background:

• The role of human herpesvirus 6B (HHV-6B) as a pulmonary pathogen post-hematopoietic cell transplant (HCT) remains unclear due to limited understanding of its immunopathogenesis.
• Pneumonia is a significant complication following allogeneic HCT, necessitating identification of causative agents.

Purpose of the Study:

• To investigate the presence and significance of HHV-6B infection in the lungs of patients undergoing allogeneic HCT with pneumonia.
• To determine if HHV-6B detection in bronchoalveolar lavage fluid (BALF) correlates with clinical outcomes and host immune responses.

Main Methods:

• A prospective multicenter study involving 116 patients who underwent bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT.
• Testing of blood and BAL fluid for HHV-6B DNA and mRNA transcripts indicative of lytic infection.
• RNA-sequencing of paired blood samples to analyze host gene expression signatures.

Main Results:

• HHV-6B DNA was detected in 37% of BAL samples, with 49% of these also showing HHV-6B mRNA.
• Established BALF HHV-6B DNA viral load thresholds accurately predicted mRNA detection and were linked to increased mortality risk, including death from respiratory failure.
• Distinct host gene expression profiles, particularly enriched interferon signaling, were observed in patients with HHV-6B DNA in BALF, especially those with idiopathic pneumonia.

Conclusions:

• These findings strongly implicate HHV-6B as a significant pulmonary pathogen in the context of allogeneic HCT.
• The detection of HHV-6B in BALF and its associated viral load are critical indicators of prognosis and mortality.
• The study highlights the importance of considering HHV-6B in the differential diagnosis of pneumonia post-HCT.