title: Role of Jumonji C-domain containing protein 6 (JMJD6) in infectivity of foot-and-mouth disease virus.
abstract: Foot-and-mouth disease virus (FMDV) utilizes four integrins (αvβ1, αvβ3, αvβ6, and αvβ8) as its primary cell receptor. During cell culture propagation, FMDV frequently adapts to use heparan sulfate (HS), and rarely utilizes an unidentified third receptor. Capsid mutations acquired by a soluble integrin resistant FMDV cause (i) adaptation to CHO-677 cells (ii) increased affinity to membrane-bound Jumonji C-domain containing protein 6 (JMJD6) (iii) induced JMJD6 re-localization from the cell surface and cytoplasm to the nucleus. Interestingly, pre-treatment of cells with N- and C-terminal JMJD6 antibodies or by simultaneous incubation of mutant virus with soluble JMJD6 (but not by treatment with HS or αvβ6) impaired virus infectivity in cultured cells. JMJD6 and mutant virus co-purified by reciprocal co-immunoprecipitation. Molecular docking predictions suggested JMJD6 C-terminus interacts with mutated VP1 capsid protein. We conclude when specific VP1 mutations are displayed, JMJD6 contributes to FMDV infectivity and may be a previously unidentified FMDV receptor.
authors.affiliation: Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Lawrence
authors.affiliation: Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, United States.
authors.forename: Devendra
authors.initials: D
authors.lastname: Rai
authors.affiliation: Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, United States.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Conderino
authors.affiliation: Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, United States.
authors.forename: Sabena
authors.initials: S
authors.lastname: Uddowla
authors.affiliation: Foreign Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, United States. Electronic address: Elizabeth.Rieder@ars.usda.gov.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rieder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002522:Chlorocebus aethiops; D003412:Cricetulus; D018360:Crystallography, X-Ray; D004847:Epithelial Cells / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D016023:Integrins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000821:virology; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D036022:Capsid Proteins; D016023:Integrins; D011991:Receptors, Virus; D011994:Recombinant Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; D056484:Jumonji Domain-Containing Histone Demethylases
keywords: FMDV alternate receptor; Foot-and-mouth disease virus (FMDV); Jumonji C-domain containing protein 6 (JMJD6)