State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
J Virol. 2023 Apr 27;97(4):e0024723. doi: 10.1128/jvi.00247-23. Epub 2023 Apr 5.
The African swine fever virus (ASFV) has caused a devastating pandemic in domestic and wild swine, causing economic losses to the global swine industry. Recombinant live attenuated vaccines are an attractive option for ASFV treatment. However, safe and effective vaccines against ASFV are still scarce, and more high-quality experimental vaccine strains need to be developed. In this study, we revealed that deletion of the ASFV genes , , and from the highly virulent isolate ASFV CN/GS/2018 (ASFV-GS) substantially attenuated virulence in swine. Pigs infected with 10 50% hemadsorbing doses of the virus with these gene deletions remained healthy during the 19-day observation period. No ASFV infection was detected in contact pigs under the experimental conditions. Importantly, the inoculated pigs were protected against homologous challenges. Additionally, RNA sequence analysis showed that deletion of these viral genes induced significant upregulation of the host histone H3.1 gene () and downregulation of the ASFV gene. Knocking down the expression of resulted in high levels of ASFV replication in primary porcine macrophages . These findings indicate that the deletion mutant virus ASFV-GS-Δ18R/NL/UK is a novel potential live attenuated vaccine candidate and one of the few experimental vaccine strains reported to induce full protection against the highly virulent ASFV-GS virus strain. Ongoing outbreaks of African swine fever (ASF) have considerably damaged the pig industry in affected countries. Thus, a safe and effective vaccine is important to control African swine fever spread. Here, an ASFV strain with three gene deletions was developed by knocking out the viral genes (), (), and (). The results showed that the recombinant virus was completely attenuated in pigs and provided strong protection against parental virus challenge. Additionally, no viral genomes were detected in the sera of pigs housed with animals infected with the deletion mutant. Furthermore, transcriptome sequencing (RNA-seq) analysis revealed significant upregulation of histone H3.1 in virus-infected macrophage cultures and downregulation of the ASFV gene after viral , , and deletion. Our study provides a valuable live attenuated vaccine candidate and potential gene targets for developing strategies for anti-ASFV treatment.
非洲猪瘟病毒（ASFV）已在国内外猪群中引发了毁灭性的大流行，给全球养猪业造成了经济损失。重组活减毒疫苗是治疗 ASFV 的一种有吸引力的选择。然而，针对 ASFV 的安全有效的疫苗仍然稀缺，需要开发更多高质量的实验性疫苗株。在本研究中，我们揭示了从高毒力分离株 ASFV CN/GS/2018（ASFV-GS）中缺失 ASFV 基因 、 、 和 可显著降低病毒在猪体内的毒力。在 19 天的观察期内，感染这些基因缺失病毒的猪在 10 50%血凝剂量下仍保持健康。在实验条件下，接触猪未检测到 ASFV 感染。重要的是，接种猪可免受同源性挑战的保护。此外，RNA 序列分析显示，这些病毒基因的缺失诱导了宿主组蛋白 H3.1 基因（）的显著上调和 ASFV 基因的下调。敲低 基因的表达导致猪原代巨噬细胞中 ASFV 的大量复制。这些发现表明，缺失突变病毒 ASFV-GS-Δ18R/NL/UK 是一种新型潜在的活减毒疫苗候选株，是少数能诱导对高毒力 ASFV-GS 病毒株完全保护的实验性疫苗株之一。非洲猪瘟（ASF）的持续爆发对受影响国家的养猪业造成了巨大损害。因此，安全有效的疫苗对于控制非洲猪瘟的传播至关重要。在这里，通过敲除病毒基因 （）、 （）和 （），开发了一株具有三个基因缺失的 ASFV 株。结果表明，重组病毒在猪体内完全减毒，并能为亲本病毒攻击提供强有力的保护。此外，在与感染缺失突变的动物饲养的猪的血清中未检测到病毒基因组。此外，转录组测序（RNA-seq）分析显示，在病毒感染的巨噬细胞培养物中组蛋白 H3.1 显著上调，而在病毒 、 、 和 缺失后 ASFV 基因下调。我们的研究为开发抗 ASFV 治疗策略提供了一种有价值的活减毒疫苗候选株和潜在的基因靶点。
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