title: Deletion of African swine fever virus interferon inhibitors from the genome of a virulent isolate reduces virulence in domestic pigs and induces a protective response.
abstract: African swine fever virus (ASFV) encodes multiple copies of MGF360 and MGF530/505 gene families. These genes have been implicated in the modulation of the type I interferon (IFN) response. We investigated the effect of modulating the IFN response on virus attenuation and induction of protective immunity by deleting genes MGF360 (MGF360-10L, 11L, 12L, 13L, 14L) and MGF530/505 (MGF530/505-1R, 2R and 3R) and interrupting genes (MGF360-9L and MGF530/505-4R) in the genome of the virulent ASFV isolate Benin 97/1. Replication of this deletion mutant, BeninΔMGF, in porcine macrophages in vitro was similar to that of the parental virulent virus Benin 97/1 and the natural attenuated isolate OURT88/3, which has a similar deletion of MGF360 and 530/505 genes. Levels of IFN-β mRNA in macrophages infected with virulent Benin 97/1 isolate were barely detectable but high levels were detected in macrophages infected with OURT88/3 and intermediate levels in macrophages infected with BeninΔMGF. The data confirms that these MGF360 and MGF530/505 genes have roles in suppressing induction of type I IFN. Immunisation and boost of pigs with BeninΔMGF showed that the virus was attenuated and all pigs (5/5) were protected against challenge with a lethal dose of virulent Benin 97/1. A short transient fever was observed at day 5 or 6 post-immunisation but no other clinical signs. Following immunisation and boost with the OURT88/3 isolate 3 of 4 pigs were protected against challenge. Differences were observed in the cellular and antibody responses in pigs immunised with BeninΔMGF compared to OURT88/3. Deletion of IFN modulators is a promising route for construction of rationally attenuated ASFV candidate vaccine strains.
authors: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK. Electronic address: ana.reis@pirbright.ac.uk.
authors: Ana Luisa
authors: AL
authors: Reis
authors: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors: Charles C
authors: CC
authors: Abrams
authors: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors: Lynnette C
authors: LC
authors: Goatley
authors: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors: Chris
authors: C
authors: Netherton
authors: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors: Dave G
authors: DG
authors: Chapman
authors: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors: Pedro
authors: P
authors: Sanchez-Cordon
authors: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors: Linda K
authors: LK
authors: Dixon
mesh_terms: D000357:African Swine Fever / Q000276:immunology / Q000517:prevention & control*; D000358:African Swine Fever Virus / Q000235:genetics / Q000472:pathogenicity*; D000818:Animals; D016207:Cytokines / Q000097:blood; D017353:Gene Deletion; D005814:Genes, Viral; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D016899:Interferon-beta / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D034421:Sus scrofa; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000627:therapeutic use; D019562:Viral Load; D014765:Viral Vaccines / Q000627:therapeutic use*; D014774:Virulence
chemical_list: D016207:Cytokines; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D016899:Interferon-beta
keywords: ASFV; Attenuation; Interferon; MGF360; MGF530/505