title: Pathogen receptor discovery with a microfluidic human membrane protein array.
abstract: The discovery of how a pathogen invades a cell requires one to determine which host cell receptors are exploited. This determination is a challenging problem because the receptor is invariably a membrane protein, which represents an Achilles heel in proteomics. We have developed a universal platform for high-throughput expression and interaction studies of membrane proteins by creating a microfluidic-based comprehensive human membrane protein array (MPA). The MPA is, to our knowledge, the first of its kind and offers a powerful alternative to conventional proteomics by enabling the simultaneous study of 2,100 membrane proteins. We characterized direct interactions of a whole nonenveloped virus (simian virus 40), as well as those of the hepatitis delta enveloped virus large form antigen, with candidate host receptors expressed on the MPA. Selected newly discovered membrane protein-pathogen interactions were validated by conventional methods, demonstrating that the MPA is an important tool for cellular receptor discovery and for understanding pathogen tropism.
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, 5290002, Israel;
authors.forename: Yair
authors.initials: Y
authors.lastname: Glick
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, 5290002, Israel;
authors.forename: Ya'ara
authors.initials: Y
authors.lastname: Ben-Ari
authors.affiliation: Faculty of Medicine, Hebrew University, Jerusalem, 9112001, Israel;
authors.forename: Nir
authors.initials: N
authors.lastname: Drayman
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, 5290002, Israel;
authors.forename: Michal
authors.initials: M
authors.lastname: Pellach
authors.affiliation: Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Gregory
authors.initials: G
authors.lastname: Neveu
authors.affiliation: Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Jim
authors.initials: J
authors.lastname: Boonyaratanakornkit
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, 5290002, Israel;
authors.forename: Dorit
authors.initials: D
authors.lastname: Avrahami
authors.affiliation: Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Shirit
authors.initials: S
authors.lastname: Einav
authors.affiliation: Faculty of Medicine, Hebrew University, Jerusalem, 9112001, Israel;
authors.forename: Ariella
authors.initials: A
authors.lastname: Oppenheim
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, 5290002, Israel; doron.gerber@biu.ac.il.
authors.forename: Doron
authors.identifier: http://orcid.org/0000-0002-0532-2928
authors.initials: D
authors.lastname: Gerber
mesh_terms: D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D011991:Receptors, Virus / Q000378:metabolism*; D013539:Simian virus 40 / Q000378:metabolism*
chemical_list: D011991:Receptors, Virus
keywords: integrated microfluidics; membrane protein array; pathogen–host interactions; receptor discovery