Bidirectional transfer of human cytomegalovirus strains in donor and recipient seropositive lung transplant patients.
donor recipient origin
genotyping
human cytomegalovirus
lung transplantation
strain diversity
virus tracing
Journal
Journal of medical virology
ISSN: 1096-9071
Titre abrégé: J Med Virol
Pays: United States
ID NLM: 7705876
Informations de publication
Date de publication:
Jul 2024
Jul 2024
Historique:
revised:
29
05
2024
received:
30
03
2024
accepted:
11
06
2024
medline:
1
7
2024
pubmed:
1
7
2024
entrez:
1
7
2024
Statut:
ppublish
Résumé
Donor and recipient human cytomegalovirus (HCMV) seropositive (D+R+) lung transplant recipients (LTRs) often harbor multiple strains of HCMV, 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 before transplantation. HCMV strains were characterized by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first 6 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, indicating replication of both sources despite pre-existing immunity.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29770Subventions
Organisme : Austrian Science Fund
ID : P31503-B26
Informations de copyright
© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.
Références
Sijmons S, Thys K, Mbong Ngwese M, et al. High‐throughput analysis of human cytomegalovirus genome diversity highlights the widespread occurrence of gene‐disrupting mutations and pervasive recombination. J Virol. 2015;89(15):7673‐7695.
Lassalle F, Depledge DP, Reeves MB, et al. Islands of linkage in an ocean of pervasive recombination reveals two‐speed evolution of human cytomegalovirus genomes. Virus Evol. 2016;2(1):vew017.
Suárez NM, Wilkie GS, Hage E, et al. Human cytomegalovirus genomes sequenced directly from clinical material: variation, multiple‐strain infection, recombination, and gene loss. J Infect Dis. 2019;220(5):781‐791.
Wang HY, Valencia SM, Pfeifer SP, Jensen JD, Kowalik TF, Permar SR. Common polymorphisms in the glycoproteins of human cytomegalovirus and associated strain‐specific immunity. Viruses. 2021;13(6):1106.
Cagliani R, Forni D, Mozzi A, Sironi M. Evolution and genetic diversity of primate cytomegaloviruses. Microorganisms. 2020;8(5):624.
Puchhammer‐Stöckl E, Görzer I. Human cytomegalovirus: an enormous variety of strains and their possible clinical significance in the human host. Future Virol. 2011;6(2):259‐271.
Hage E, Wilkie GS, Linnenweber‐Held S, et al. Characterization of human cytomegalovirus genome diversity in immunocompromised hosts by whole genomic sequencing directly from clinical specimens. J Infect Dis. 2017;215(11):1673‐1683.
Cudini J, Roy S, Houldcroft CJ, et al. Human cytomegalovirus haplotype reconstruction reveals high diversity due to superinfection and evidence of within‐host recombination. Proc Nat Acad Sci. 2019;116(12):5693‐5698.
Dhingra A, Götting J, Varanasi PR, et al. Human cytomegalovirus multiple‐strain infections and viral population diversity in haematopoietic stem cell transplant recipients analysed by high‐throughput sequencing. Med Microbiol Immunol. 2021;210(5‐6):291‐304.
Götting J, Lazar K, Suárez NM, et al. Human cytomegalovirus genome diversity in longitudinally collected breast milk samples. Front Cell Infect Microbiol. 2021;11:664247.
Coaquette A, Bourgeois A, Dirand C, Varin A, Chen W, Herbein G. Mixed cytomegalovirus glycoprotein B genotypes in immunocompromised patients. Clin Infect Dis. 2004;39(2):155‐161.
Lisboa LF, Tong Y, Kumar D, et al. Analysis and clinical correlation of genetic variation in cytomegalovirus. Transpl Infect Dis. 2011;14(2):132‐140.
Puchhammer‐Stöckl E, Görzer I, Zoufaly A, et al. Emergence of multiple cytomegalovirus strains in blood and lung of lung transplant recipients. Transplantation. 2006;81(2):187‐194.
Houldcroft CJ, Bryant JM, Depledge DP, et al. Detection of low frequency multi‐drug resistance and novel putative maribavir resistance in immunocompromised pediatric patients with cytomegalovirus. Front Microbiol. 2016;7:1317.
Griffiths P, Reeves M. Pathogenesis of human cytomegalovirus in the immunocompromised host. Nat Rev Microbiol. 2021;19(12):759‐773.
Sinclair J, Poole E. Human cytomegalovirus latency and reactivation in and beyond the myeloid lineage. Future Virol. 2014;9(6):557‐563.
Poole E, Juss JK, Krishna B, Herre J, Chilvers ER, Sinclair J. Alveolar macrophages isolated directly from human cytomegalovirus (HCMV)‐seropositive individuals are sites of HCMV reactivation in vivo. J Infect Dis. 2015;211(12):1936‐1942.
Eguiluz‐Gracia I, Schultz HH, Sikkeland LI, et al. Long‐term persistence of human donor alveolar macrophages in lung transplant recipients. Thorax. 2016;71(11):1006‐1011.
Wiebe BM, Mortensen SA, Petterson G, Svendsen UG, Andersen CB. Macrophage and lymphocyte chimerism in bronchoalveolar lavage cells from human lung allograft recipients. APMIS. 2001;109(6):435‐440.
Manuel O, Pang XL, Humar A, Kumar D, Doucette K, Preiksaitis JK. An assessment of donor‐to‐recipient transmission patterns of human cytomegalovirus by analysis of viral genomic variants. J Infect Dis. 2009;199(11):1621‐1628.
Hasing ME, Pang XL, Mabilangan C, Preiksaitis JK. Donor cytomegalovirus transmission patterns in solid organ transplant recipients with primary infection. J Infect Dis. 2021;223(5):827‐837.
Kulekci B, Schwarz S, Brait N, et al. Human cytomegalovirus strain diversity and dynamics reveal the donor lung as a major contributor after transplantation. Virus Evol. 2022;8(2):veac076.
Görzer I, Guelly C, Trajanoski S, Puchhammer‐Stöckl E. Deep sequencing reveals highly complex dynamics of human cytomegalovirus genotypes in transplant patients over time. J Virol. 2010;84(14):7195‐7203.
Chou S. Neutrallzing antibody responses to reinfecting strains of cytomegalovirus in transplant recipients. J Infect Dis. 1989;160(1):16‐21.
Grundy J, Super M, Sweny P, et al. Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. The Lancet. 1988;332(8603):132‐135.
Speck NE, Schuurmans MM, Murer C, Benden C, Huber LC. Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology. Respir Res. 2016;17(1):74.
Brait N, Külekçi B, Goerzer I. Long range PCR‐based deep sequencing for haplotype determination in mixed HCMV infections. BMC Genomics. 2022;23(1):31.
Yan H, Koyano S, Inami Y, et al. Genetic linkage among human cytomegalovirus glycoprotein N (gN) and gO genes, with evidence for recombination from congenitally and post‐natally infected Japanese infants. J Gen Virol. 2008;89(Pt 9):2275‐2279.
Nelson CS, Vera Cruz D, Su M, et al. Intrahost dynamics of human cytomegalovirus variants acquired by seronegative glycoprotein B vaccinees. J Virol. 2019;93(5):e01695‐18.
Gerna G, Lilleri D, Fornara C, d'Angelo P, Baldanti F. Relationship of human cytomegalovirus‐infected endothelial cells and circulating leukocytes in the pathogenesis of disseminated human cytomegalovirus infection: a narrative review. Rev Med Virol. 2024;34(1):e2496.
Braun B, Sinzger C. Transmission of cell‐associated human cytomegalovirus isolates between various cell types using polymorphonuclear leukocytes as a vehicle. Med Microbiol Immunol. 2021;210(4):197‐209.
Clarke LM, Daidone BJ, Inghida R, Kirwin M, Sierra MF. Differential recovery of cytomegalovirus from cellular and supernatant components of bronchoalveolar lavage specimens. Am J Clin Path. 1992;97(3):313‐317.
Nayak DK, Zhou F, Xu M, et al. Long‐term persistence of donor alveolar macrophages in human lung transplant recipients that influences donor‐specific immune responses. Am J Transplant (AJT). 2016;16(8):2300‐2311.
Bittmann I, Dose T, Baretton GB, et al. Cellular chimerism of the lung after transplantation. an interphase cytogenetic study. Am J Clin Path. 2001;115(4):525‐533.
Byrne AJ, Powell JE, O'Sullivan BJ, et al. Dynamics of human monocytes and airway macrophages during healthy aging and after transplant. J Exp Med. 2020;217(3):e20191236.
Snyder ME, Bondonese A, Craig A, et al. Rate of recipient‐derived alveolar macrophage development and major histocompatibility complex cross‐decoration after lung transplantation in humans. Am J Transplant (AJT). 2022;22(2):574‐587.
Kalser J, Adler B, Mach M, Kropff B, Puchhammer‐Stöckl E, Görzer I. Differences in growth properties among two human cytomegalovirus glycoprotein O genotypes. Front Microbiol. 2017;8:1609.