Metagenomic sequencing reveals time, host, and body compartment-specific viral dynamics after lung transplantation

Abstract

Background: The virome of lung transplant recipients (LTRs) under immunosuppressive therapy is dominated by non-pathogenic Anelloviridae and further includes several pathogenic viruses such as Herpesviruses or respiratory viruses. It is unclear whether the donor-derived virome in the transplanted lung influences recipient virome dynamics in other body compartments and if so, to which degree. Likewise, it is unknown whether dependencies exist among virus populations that mutually shape viral loads and kinetics. Results: To address these questions, we characterized viral communities in airways and plasma of 49 LTRs and analyzed their abundance patterns in a data modeling approach. We found distinct viral clusters that were specific for body compartments and displayed independent dynamics. These clusters robustly gathered specific viral species across the patient cohort. In the lung, viral cluster abundance associated with time after transplantation and we detected mutual exclusion of viral species within the same human host. In plasma, viral cluster dynamics were associated with the indication for transplantation lacking significant short-time changes. Interestingly, pathogenic viruses in the plasma co-occurred specifically with Alpha torque virus genogroup 4 and Gamma torque virus strains suggesting shared functional or ecological requirements. Conclusions: In summary, the detailed analysis of virome dynamics after lung transplantation revealed host, body compartment, and time-specific dependency patterns among viruses. Furthermore, our results suggested genetic adaptation to the host microenvironment at the level of the virome and support the hypothesis of functional complementarity between Anellovirus groups and other persistent viruses. [MediaObject not available: see fulltext.].