title: Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus.
abstract: African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically deleting virus genes involved in virulence, including the thymidine kinase (TK) gene. TK has been shown to be involved in the virulence of several viruses, including ASFV. Here we report the construction of a recombinant virus (ASFV-G/V-ΔTK) obtained by deleting the TK gene in a virulent strain of ASFV Georgia adapted to replicate in Vero cells (ASFV-G/VP30). ASFV-G/P-ΔTK demonstrated decreased replication both in primary swine macrophage cell cultures and in Vero cells compared with ASFV-G/VP30. In vivo, intramuscular administration of up to 10(6) TCID50 of ASFV-G/V-ΔTK does not result in ASF disease. However, these animals are not protected when challenged with the virulent parental Georgia strain.
authors.affiliation: Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: B
authors.initials: B
authors.lastname: Sanford
authors.affiliation: Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: L G
authors.initials: LG
authors.lastname: Holinka
authors.affiliation: Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA; Department of Pathobiology and Veterinary Science, CANR, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: V
authors.initials: V
authors.lastname: O'Donnell
authors.affiliation: Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Krug
authors.affiliation: Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: J
authors.initials: J
authors.lastname: Carlson
authors.affiliation: Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: M
authors.initials: M
authors.lastname: Alfano
authors.affiliation: APHIS, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: C
authors.initials: C
authors.lastname: Carrillo
authors.affiliation: APHIS, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: APHIS, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Lowe
authors.affiliation: Department of Pathobiology and Veterinary Science, CANR, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Risatti
authors.affiliation: Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Gladue
authors.affiliation: Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, NY 11944, USA. Electronic address: manuel.borca@ars.usda.gov.
authors.forename: M V
authors.initials: MV
authors.lastname: Borca
mesh_terms: D000357:African Swine Fever / Q000473:pathology* / Q000821:virology; D000358:African Swine Fever Virus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D000818:Animals; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000821:virology; D017353:Gene Deletion; D007273:Injections, Intramuscular; D008264:Macrophages / Q000821:virology; D013552:Swine; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014709:Vero Cells; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D037521:Virulence Factors; D013937:Thymidine Kinase
keywords: ASFV; African swine fever virus; Thymidine kinase