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Bidirectional transfer of human cytomegalovirus strains in donor and recipient seropositive lung transplant patients
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  • Büsra Külekci,
  • Madlen Mollik,
  • Stefan Schwarz,
  • Nicole Perkmann-Nagele,
  • Silvana Geleff,
  • Peter Jaksch,
  • Konrad Hoetzenecker,
  • Christopher Lambers,
  • Elisabeth Puchhammer-Stoeckl,
  • Irene Goerzer
Büsra Külekci
Medizinische Universitat Wien Department fur Virologie
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Madlen Mollik
Medizinische Universitat Wien Department fur Virologie
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Stefan Schwarz
Medical University of Vienna Center for Brain Research
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Nicole Perkmann-Nagele
Medical University of Vienna Center for Brain Research
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Silvana Geleff
Medical University of Vienna Center for Brain Research
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Peter Jaksch
Medical University of Vienna Center for Brain Research
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Konrad Hoetzenecker
Medical University of Vienna Center for Brain Research
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Christopher Lambers
Medical University of Vienna Center for Brain Research
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Elisabeth Puchhammer-Stoeckl
Medizinische Universitat Wien Department fur Virologie
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Irene Goerzer
Medizinische Universitat Wien Department fur Virologie

Corresponding Author:[email protected]

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Abstract

Donor and recipient HCMV-seropositive (D+R+) lung transplant recipients (LTRs) often harbour multiple human cytomegalovirus (HCMV) strains, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post-transplantation (post-Tx) strain population is unknown. Here, we deciphered the D and R origin of the post-Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin-fixed paraffin-embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained prior to transplantation. HCMV strains were characterised by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first six months after transplantation, likely by infiltrating CD14+ CD163+/- alveolar macrophages. In three LTRs, we demonstrate both rapid D-strain dissemination and persistence in the transplanted lung for >1 year post-Tx. Broad inter-host diversity contrasts with intra-host genotype sequence stability upon transmission, during follow-up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long‑term in subsequent episodes of infection, suggesting no replication advantage of one source over the other despite pre-existing R strain-specific immunity.
Submitted to Journal of Medical Virology
02 Apr 2024Reviewer(s) Assigned
24 Apr 2024Review(s) Completed, Editorial Evaluation Pending
24 Apr 2024Editorial Decision: Revise Minor
29 May 20241st Revision Received
30 May 2024Submission Checks Completed
30 May 2024Assigned to Editor
30 May 2024Reviewer(s) Assigned
11 Jun 2024Review(s) Completed, Editorial Evaluation Pending