title: Characterization of a chimeric foot-and-mouth disease virus bearing a bovine rhinitis B virus leader proteinase.
abstract: Bovine rhinitis B virus (BRBV) shares many motifs and sequence similarities with foot-and-mouth disease virus (FMDV). This study examined if the BRBV leader proteinase (L(pro) ) could functionally replace that of FMDV. A mutant A24LBRV3DYR FMDV engineered with the BRBV L(pro) and an antigenic marker in the 3D polymerase exhibited growth properties and eIF4G cleavage similar to parental A24WT virus. The A24LBRV3DYR type I interferon activity in infected bovine cells resembled that of A24LL virus that lacks L(pro), but this effect was less pronounced for A24LBRV3DYR infected porcine cells. In vivo studies showed that the A24LBRV3DYR virus was attenuated in cattle, and exhibited low virulence in pigs exposed by direct contact. The mutant virus induced protective immunity in cattle against challenge with parental A24WT. These results provide evidence that L(pro) of different Aphthoviruses are not fully functionally interchangeable and have roles that may depend on the nature of the infected host.
authors.affiliation: Foreign Animal Disease Research Unit, United States Department of Agriculture, Agricultural Research Service, Plum Island Animal Disease Center, Greenport, NY 11944, United States.
authors.forename: Sabena
authors.initials: S
authors.lastname: Uddowla
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pacheco
authors.forename: Christopher
authors.initials: C
authors.lastname: Larson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bishop
authors.forename: Luis L
authors.initials: LL
authors.lastname: Rodriguez
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Rai
authors.forename: Jonathan
authors.initials: J
authors.lastname: Arzt
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rieder
mesh_terms: D000818:Animals; D005537:Aphthovirus / Q000235:genetics*; D002417:Cattle; D002418:Cattle Diseases / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D002460:Cell Line; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D005536:Foot-and-Mouth Disease / Q000473:pathology / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D008958:Models, Molecular; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000473:pathology / Q000821:virology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D039603:Eukaryotic Initiation Factor-4G; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D010450:Endopeptidases; C088747:leader proteinase, foot-and-mouth disease virus
keywords: Bovine rhinitis B virus (BRBV) leader proteinase; Chimeric foot-and-mouth disease virus (FMDV); FMDV pathogenesis