Epstein-Barr Virus Lytic Transcripts Correlate with the Degree of Myocardial Inflammation in Heart Failure Patients

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment.