title: Pathogenesis and micro-anatomic characterization of a cell-adapted mutant foot-and-mouth disease virus in cattle: Impact of the Jumonji C-domain containing protein 6 (JMJD6) and route of inoculation.
abstract: A companion study reported Jumonji-C domain containing protein 6 (JMJD6) is involved in an integrin- and HS-independent pathway of FMDV infection in CHO cells. JMJD6 localization was investigated in animal tissues from cattle infected with either wild type A24-FMDV (A24-WT) or mutant FMDV (JMJD6-FMDV) carrying E95K/S96L and RGD to KGE mutations in VP1. Additionally, pathogenesis of mutant JMJD6-FMDV was investigated in cattle through aerosol and intraepithelial lingual (IEL) inoculation. Interestingly, JMJD6-FMDV pathogenesis was equivalent to A24-WT administered by IEL route. In contrast, JMJD6-FMDV aerosol-infected cattle did not manifest signs of FMD and animals showed no detectable viremia. Immunofluorescent microscopy of post-mortem tissue revealed JMJD6-FMDV exclusively co-localized with JMJD6(+) cells while A24-WT was occasionally found in JMJD6(+) cells. In vitro, chemical uptake inhibitors demonstrated JMJD6-FMDV entered cells via clathrin-coated pit endocytosis. In vivo, JMJD6-FMDV exhibited preference for JMJD6(+) cells, but availability of this alternative receptor likely depends on route of inoculation.
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: Juan
authors.initials: J
authors.lastname: Pacheco
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: Carolina
authors.initials: C
authors.lastname: Stenfeldt
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: Jonathan
authors.initials: J
authors.lastname: Arzt
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 K
authors.initials: DK
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. Electronic address: Elizabeth.Rieder@ars.usda.gov.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rieder
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D002460:Cell Line; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D003412:Cricetulus; D004705:Endocytosis; D004847:Epithelial Cells / Q000821:virology; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016296:Mutagenesis; D009154:Mutation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014059:Tongue; D014611:Vaccination
chemical_list: D016023:Integrins; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D011994:Recombinant Proteins; D056484:Jumonji Domain-Containing Histone Demethylases
keywords: FMDV third receptor; Foot-and-mouth disease virus (FMDV); Jumonji C-domain containing protein 6 (JMJD6); Viral pathogenesis