Human cytomegalovirus strain diversity and dynamics reveal the donor lung as a major contributor after transplantation. Issue 2 (24th August 2022)

• Record Type: Journal Article
• Authors: Külekci, Büsra; Schwarz, Stefan; Brait, Nadja; Perkmann-Nagele, Nicole; Jaksch, Peter; Hoetzenecker, Konrad; Puchhammer-Stöckl, Elisabeth; Goerzer, Irene
• Is Part Of: Virus evolution. Volume 8:Issue 2(2022)
• Publication Date: 2022-08-24
• Subjects: human cytomegalovirus -- intra-host strain diversity -- mixed infections -- lung transplant -- viral strain dynamics -- PacBio sequencing; Viruses -- Evolution -- Periodicals; 579.2138
• DOI: 10.1093/ve/veac076
• Languages: English
• ISSNs: 2057-1577

Abstract

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.