Temporal dynamics of the lung and plasma viromes in lung transplant recipients

The human virome plays an important role for the clinical outcome of lung transplant recipients (LTRs). While pathogenic viruses may cause severe infections, non-pathogenic viruses may serve as potential markers for the level of immunosuppression. However, neither the complexity of the virome in different compartments nor the dynamics of the virus populations posttransplantation are yet understood. Therefore, in this study the virome was analyzed by metagenomic sequencing in simultaneously withdrawn bronchoalveolar lavage (BAL) and plasma samples of 15 LTRs. In seven patients, also follow-up samples were investigated for abundance and dynamics of virus populations posttransplantation. Five eukaryotic and two prokaryotic virus families were identified in BAL, and nine eukaryotic and two prokaryotic families in plasma. Anelloviruses were the most abundant in both compartments, followed by Herpes-and Coronaviruses. Virus abundance was significantly higher in LTRs than in healthy controls (Kruskal-Wallis test, p<0.001). Up to 48 different anellovirus strains were identified within a single LTR. Analyses in the follow-up patients revealed for the first time a highly complex and unique dynamics of individual anellovirus strains in the posttransplantation period. The abundance of anelloviruses in plasma was inversely correlated with that of other eukaryotic viruses (Pearson correlation coefficient r = -0.605; p<0.05). A broad spectrum of virus strains co-exists in BAL and plasma of LTRs. Especially for the anelloviruses, a high degree of co-infections and a highly individual and complex dynamics after transplantation was observed. The biological impact of these findings and their relation to clinical variables remain to be elucidated by future analyses.