Human cytomegalovirus strain diversity and dynamics reveal the donor lung as a major contributor after transplantation

Büsra Külekci, Stefan Schwarz, Nadja Brait, Nicole Perkmann-Nagele, Peter Jaksch, Konrad Hoetzenecker, Elisabeth Puchhammer-Stöckl, Irene Goerzer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

Mixed human cytomegalovirus (HCMV) strain infections are frequent in lung transplant recipients (LTRs). To date, the influence of the donor (D) and recipient (R) HCMV serostatus on intra-host HCMV strain composition and viral population dynamics after transplantation is only poorly understood. Here, we investigated ten pre-transplant lungs from HCMV-seropositive donors and 163 sequential HCMV-DNA-positive plasma and bronchoalveolar lavage samples from fifty LTRs with multiviremic episodes post-transplantation. The study cohort included D+R+ (38 per cent), D+R− (36 per cent), and D−R+ (26 per cent) patients. All samples were subjected to quantitative genotyping by short amplicon deep sequencing, and twenty-four of them were additionally PacBio long-read sequenced for genotype linkages. We find that D+R+ patients show a significantly elevated intra-host strain diversity compared to D+R− and D−R+ patients (P = 0.0089). Both D+ patient groups display significantly higher viral population dynamics than D− patients (P = 0.0061). Five out of ten pre-transplant donor lungs were HCMV DNA positive, whereof three multiple HCMV strains were detected, indicating that multi-strain transmission via lung transplantation is likely. Using long reads, we show that intra-host haplotypes can share distinctly linked genotypes, which limits overall intra-host diversity in mixed infections. Together, our findings demonstrate donor-derived strains as the main source of increased HCMV strain diversity and dynamics post-transplantation. These results foster strategies to mitigate the potential transmission of the donor strain reservoir to the allograft, such as ex vivo delivery of HCMV-selective immunotoxins prior to transplantation to reduce latent HCMV.

Original languageEnglish
Article numberveac076
Number of pages13
JournalVirus Evolution
Volume8
Issue number2
DOIs
Publication statusPublished - 2022

Keywords

  • human cytomegalovirus
  • intra-host strain diversity
  • lung transplant
  • mixed infections
  • PacBio sequencing
  • viral strain dynamics

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