African swine fever (ASF) is an acute, febrile, and highly contagious infectious disease of swine with the etiological agent of African swine fever virus (ASFV). The mortality rate of virulent strains is as high as 100%. Strengthening biosafety is so far the most effective way to prevent and control ASF. Therefore, it is urgent to develop a safe and effective vaccine. In this study, a Genotype II live‐attenuated ASF vaccine bearing 24 genes deletion in 3 independent regions was constructed based on the highly virulent Eurasian strain ASFV CN/GS 2018 backbone. The resulting mutant ASFV‐Δ24 is characterized by complete deletion of 24 genes distributed in 3 genomic positions of 852 to 11 468, 19 732 to 22 929, and 179 519 to 180 617, among which MGF100 and whole MGF300 families are pioneeringly removed. The ASFV‐Δ24 displayed a delayed and reduced replication kinetics as well as aberrant icosahedral empty particles devoid of a nucleoid when compared to the parental virus. Animal experiments showed that ASFV‐Δ24 was completely attenuated in animals as evidenced by stable body temperature and no ASF‐compatible clinical signs in vaccinated pigs. The ASFV‐Δ24 could provide complete homologous protection against lethal challenge, as vaccinated pigs demonstrated boosted antibody response, transient but low levels of viremia in blood and virus titers in organs as well as almost undetectable viral shedding. Gene deletions in multiple regions are helpful for prevention of virulence reversion. These results indicate that ASFV‐Δ24 can be used as an effective and promising candidate vaccine to control the spread of ASFV.
Fan Xu, Wen Dang, Yu Du et al.· The FASEB Journal· 0 citations
The internal ribosome entry site (IRES) is a cis‐acting element found in certain RNA viruses. In virus‐infected cells, the Senecavirus A (SVA) IRES can directly recruit the small ribosomal subunit to an internal initiation codon on the mRNA, enabling translation initiation independently of both the 5′ cap structure of the viral genome and the host cell eukaryotic initiation factor 4F (eIF4F). As a small RNA virus, SVA frequently accumulates genetic mutations during transmission. This study aimed to characterize the mutational and evolutionary patterns of the SVA genome during its transmission within host cells exhibiting enhanced innate immunity. SVA was serially passaged for 80 generations in preactivated 3D4/21 cells that had been established in an antiviral innate immune state. During serial passaging, two stable single‐nucleotide mutations were consistently identified in the IRES region of the viral genomic RNA from passages 60–80: a uridine (U) insertion at genomic position 109, and a guanine (G)‐to‐adenine (A) substitution at position 265. Furthermore, the rescued SVA mutants harboring these mutations exhibited significantly higher replication titers than the parental strain. Notably, our results indicated that the mutant virus was unable to evade host antiviral innate immunity, whereas it significantly enhanced the translational activity of the SVA IRES. Collectively, these findings provide a foundation for understanding how single nucleotide polymorphisms (SNPs) in the 5′ untranslated region (UTR) region influence viral IRES activity and the replication capacity of recombinant viruses.
Tao Li, Wen Dang, Weiwei Li et al.· Transboundary and Emerging D...· 0 citations
The MGF100 family is a potential multigene-deleted target for ASFV live-attenuated vaccine development and was found to be capable of inducing a robust innate immune response in vitro and a consistent P30 antibody response in vivo.
Wen Dang, Fan Xu, Yu Du et al.· Virulence· 0 citations
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