title: The Perioperative Lung Transplant Virome: Torque Teno Viruses Are Elevated in Donor Lungs and Show Divergent Dynamics in Primary Graft Dysfunction.
abstract: Primary graft dysfunction (PGD) is a principal cause of early morbidity and mortality after lung transplantation, but its pathogenic mechanisms are not fully clarified. To date, studies using standard clinical assays have not linked microbial factors to PGD. We previously used comprehensive metagenomic methods to characterize viruses in lung allografts >1 mo after transplant and found that levels of Anellovirus, mainly torque teno viruses (TTVs), were significantly higher than in nontransplanted healthy controls. We used quantitative polymerase chain reaction to analyze TTV and shotgun metagenomics to characterize full viral communities in acellular bronchoalveolar lavage from donor organs and postreperfusion allografts in PGD and non-PGD lung transplant recipient pairs. Unexpectedly, TTV DNA levels were elevated 100-fold in donor lungs compared with healthy adults (p = 0.0026). Although absolute TTV levels did not differ by PGD status, PGD cases showed a smaller increase in TTV levels from before to after transplant than did control recipients (p = 0.041). Metagenomic sequencing revealed mainly TTV and bacteriophages of respiratory tract bacteria, but no viral taxa distinguished PGD cases from controls. These findings suggest that conditions associated with brain death promote TTV replication and that greater immune activation or tissue injury associated with PGD may restrict TTV abundance in the lung.
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: A A
authors.initials: AA
authors.lastname: Abbas
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.|Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: J M
authors.initials: JM
authors.lastname: Diamond
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: C
authors.initials: C
authors.lastname: Chehoud
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: B
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kotzin
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: J C
authors.initials: JC
authors.lastname: Young
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: I
authors.initials: I
authors.lastname: Imai
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: A R
authors.initials: AR
authors.lastname: Haas
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: E
authors.initials: E
authors.lastname: Cantu
authors.affiliation: Departments of Medicine and Epidemiology, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: D J
authors.initials: DJ
authors.lastname: Lederer
authors.affiliation: School of Medicine and Public Health, University of Wisconsin, Madison, WI.
authors.forename: K C
authors.initials: KC
authors.lastname: Meyer
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: R K
authors.initials: RK
authors.lastname: Milewski
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: K M
authors.initials: KM
authors.lastname: Olthoff
authors.affiliation: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: A
authors.initials: A
authors.lastname: Shaked
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.|Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: J D
authors.initials: JD
authors.lastname: Christie
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: F D
authors.identifier: http://orcid.org/0000-0003-4740-4056
authors.initials: FD
authors.lastname: Bushman
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.|Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: R G
authors.initials: RG
authors.lastname: Collman
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D016679:Genome, Viral; D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D056186:Metagenomics; D008875:Middle Aged; D019990:Perioperative Care; D055031:Primary Graft Dysfunction / Q000209:etiology* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012137:Respiratory System / Q000821:virology*; D012307:Risk Factors; D014019:Tissue Donors; D022783:Torque teno virus / Q000235:genetics*
chemical_list: D004279:DNA, Viral
keywords: immunosuppression/immune modulation; lung (allograft) function/dysfunction; lung failure/injury; lung transplantation/pulmonology; microbiomics; molecular biology; translational research/science