Viral immunology. Comprehensive serological profiling of human populations using a synthetic human virome

George J Xu; Tomasz Kula; Qikai Xu; Mamie Z Li; Suzanne D Vernon; Thumbi Ndung'u; Kiat Ruxrungtham; Jorge Sanchez; Christian Brander; Raymond T Chung; Kevin C O'Connor; Bruce Walker; H Benjamin Larman; Stephen J Elledge

doi:10.1126/science.aaa0698

Viral immunology. Comprehensive serological profiling of human populations using a synthetic human virome

Science. 2015 Jun 5;348(6239):aaa0698. doi: 10.1126/science.aaa0698.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Solve ME/CFS Initiative, Los Angeles, CA 90036, USA.
⁵ 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.
⁶ Vaccine and Cellular Immunology Laboratory, Department of Medicine, Faculty of Medicine; and Chula-Vaccine Research Center, Chulalongkorn University, Bangkok, Thailand.
⁷ Asociación Civil IMPACTA Salud y Educación, Lima, Peru.
⁸ 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.
⁹ Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁰ Department of Neurology, Yale School of Medicine, New Haven, CT 06520, USA.
¹¹ 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.
¹² Division of Immunology, Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.
¹³ 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.

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.

Publication types

Evaluation Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Antibodies, Viral / blood*
Epitopes, B-Lymphocyte / genetics
Epitopes, B-Lymphocyte / immunology*
High-Throughput Nucleotide Sequencing / methods
Host-Pathogen Interactions / immunology*
Humans
Immune System / virology*
Immunoprecipitation / methods
Peptide Library
Serologic Tests
Virus Diseases / blood
Virus Diseases / diagnosis*
Virus Diseases / immunology
Viruses / immunology*

Substances

Antibodies, Viral
Epitopes, B-Lymphocyte
Peptide Library

Abstract

Publication types

MeSH terms

Substances

Grants and funding