Bidirectional transfer of human cytomegalovirus strains in donor and
recipient seropositive lung transplant patients
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.