title: Temporal response of the human virome to immunosuppression and antiviral therapy.
abstract: There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with posttransplant therapies that combine immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients) and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma. We observe marked virome compositional dynamics at the onset of the therapy and find that the total viral load increases with immunosuppression, whereas the bacterial component of the microbiome remains largely unaffected. The data provide insight into the relationship between the human virome, the state of the immune system, and the effects of pharmacological treatment and offer a potential application of the virome state to predict immunocompetence.
authors.affiliation: Departmets of Bioengineering and Applied Physics, Stanford University and the Howard Hughes Medical Institute, Stanford, CA 94305, USA.
authors.forename: Iwijn
authors.initials: I
authors.lastname: De Vlaminck
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Khush
authors.forename: Calvin
authors.initials: C
authors.lastname: Strehl
authors.forename: Bitika
authors.initials: B
authors.lastname: Kohli
authors.forename: Helen
authors.initials: H
authors.lastname: Luikart
authors.forename: Norma F
authors.initials: NF
authors.lastname: Neff
authors.forename: Jennifer
authors.initials: J
authors.lastname: Okamoto
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Snyder
authors.forename: David N
authors.initials: DN
authors.lastname: Cornfield
authors.forename: Mark R
authors.initials: MR
authors.lastname: Nicolls
authors.forename: David
authors.initials: D
authors.lastname: Weill
authors.forename: Daniel
authors.initials: D
authors.lastname: Bernstein
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Valantine
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
mesh_terms: D000328:Adult; D019072:Antibiotic Prophylaxis; D000998:Antiviral Agents / Q000627:therapeutic use*; D001769:Blood / Q000382:microbiology / Q000821:virology*; D002648:Child; D004247:DNA / Q000097:blood / Q000235:genetics; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016040:Lung Transplantation; D014780:Viruses / Q000145:classification / Q000302:isolation & purification*
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D004247:DNA