Sensitivity of African swine fever virus to type I interferon is linked to genes within multigene families 360 and 505

Abstract

African swine fever virus (ASFV) causes a lethal haemorrhagic disease of pigs. There are conflicting reports on the role of interferon in ASFV infection. We therefore analysed the interaction of ASFV with porcine interferon, in vivo and in vitro. Virulent ASFV induced biologically active IFN in the circulation of pigs from day 3-post infection, whereas low virulent OUR T88/3, which lacks genes from multigene family (MGF) 360 and MGF505, did not. Infection of porcine leucocytes enriched for dendritic cells, with ASFV, in vitro, induced high levels of interferon, suggesting a potential source of interferon in animals undergoing acute ASF. Replication of OUR T88/3, but not virulent viruses, was reduced in interferon pretreated macrophages and a recombinant virus lacking similar genes to those absent in OUR T88/3 was also inhibited. These findings suggest that as well as inhibiting the induction of interferon, MGF360 and MGF505 genes also enable ASFV to overcome the antiviral state.

Simultaneous Deletion of the 9GL and UK Genes from the African Swine Fever Virus Georgia 2007 Isolate Offers Increased Safety and Protection against Homologous Challenge

“…Similarly, in all the animals challenged at 14 days post-ASFV-G-Δ9GL/ΔUK infection, it was possible to detect significant levels of IFN-␣ and TGF-␤. Recently, it has been reported that MGF genes play a role in blocking the IFN-␣ effect in vivo (30), suggesting a relationship between lack of MGF genes in attenuated ASFV strains and the inability of these viruses to block the host IFN-␣ response. The direct effect of IFN in inhibiting ASFV growth in vitro is controversial (30)(31)(32).…”

“…Recently, it has been reported that MGF genes play a role in blocking the IFN-␣ effect in vivo (30), suggesting a relationship between lack of MGF genes in attenuated ASFV strains and the inability of these viruses to block the host IFN-␣ response. The direct effect of IFN in inhibiting ASFV growth in vitro is controversial (30)(31)(32). Further studies are necessary to fully evaluate the role of IFN-␣ and TGF-␤ in the prevention of ASFV infection in swine to support the preliminary observation reported here.…”

Current status and evolving approaches to African swine fever vaccine development

“…Likewise, from in vitro experiments, it has been shown that the replication of Pr4 mutant lacking MGFs was significantly reduced in alveolar macrophages treated with IFN‐α (Golding et al, ). As a result, MGFs have been described to be IFN modulators and considered to be promising targets to rationally attenuate ASFV as a vaccine (Afonso et al, ; Golding et al, ; Reis et al, ). Another main host defence strategy against viral invasions is the elimination of infected cells through apoptosis (Gupta, ; Liang, Oh, & Jung, ; Nainu, Shiratsuchi, & Nakanishi, ).…”

Comparative proteomic analysis reveals different responses in porcine lymph nodes to virulent and attenuated homologous African swine fever virus strains

“…Studies about viruscells interaction have contributed significantly to unravel the mechanisms involved in pig response [3,[6][7][8][9][10]. In this regard, it has been shown that the ASFV genome encodes a large number of genes that have been identified as playing a role in host immune evasion including: interferon (IFN) inhibition by several multigene family members [11], the NF-κB and NFAT inhibitor A238L or the apoptosis inhibitor A179L, among others. All these aspects have recently been reviewed [12].…”