title: Viral immunology. Comprehensive serological profiling of human populations using a synthetic human virome.
abstract: The human virome plays important roles in health and immunity. However, current methods for detecting viral infections and antiviral responses have limited throughput and coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses. We assayed over 10(8) antibody-peptide interactions in 569 humans across four continents, nearly doubling the number of previously established viral epitopes. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Although rates of specific virus exposure were heterogeneous across populations, antibody responses targeted strongly conserved "public epitopes" for each virus, suggesting that they may elicit highly similar antibodies. VirScan is a powerful approach for studying interactions between the virome and the immune system.
authors.affiliation: Program in Biophysics, Harvard University, Cambridge, MA 02115, USA. Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Cambridge, MA 02139, USA. Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Xu
authors.affiliation: Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02115, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kula
authors.affiliation: Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA.
authors.forename: Qikai
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA.
authors.forename: Mamie Z
authors.initials: MZ
authors.lastname: Li
authors.affiliation: Solve ME/CFS Initiative, Los Angeles, CA 90036, USA.
authors.forename: Suzanne D
authors.initials: SD
authors.lastname: Vernon
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, Durban, South Africa. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard University, Cambridge, MA 02139, USA. Max Planck Institute for Infection Biology, Chariteplatz, D-10117 Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: Vaccine and Cellular Immunology Laboratory, Department of Medicine, Faculty of Medicine; and Chula-Vaccine Research Center, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.affiliation: Asociación Civil IMPACTA Salud y Educación, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: AIDS Research Institute-IrsiCaixa and AIDS Unit, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, Durban, South Africa. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard University, Cambridge, MA 02139, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Walker
authors.affiliation: Division of Immunology, Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: H Benjamin
authors.initials: HB
authors.lastname: Larman
authors.affiliation: Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA. Solve ME/CFS Initiative, Los Angeles, CA 90036, USA. selledge@genetics.med.harvard.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000821:virology*; D047468:Immunoprecipitation / Q000379:methods; D019151:Peptide Library; D012698:Serologic Tests; D014777:Virus Diseases / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D014780:Viruses / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D019151:Peptide Library