Agricultural Research Service, U.S. Department of Agriculture, Plum Island Animal Disease Center, Greenport, New York, USA.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
J Virol. 2022 Jul 27;96(14):e0054522. doi: 10.1128/jvi.00545-22. Epub 2022 Jul 6.
African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), a devastating disease affecting domestic and wild swine and currently causing a global pandemic, severely affecting swine production. Here, we demonstrate that the deletion of the previously uncharacterized ASFV gene, H108R from the highly virulent ASFV-Georgia2007 (ASFV-G) genome strain, reduces virulence in domestic swine. ASFV-G-ΔH108R, a recombinant virus with the H108R gene deleted, was used to evaluate the involvement of the H108R gene for ASFV replication and virulence in swine. ASFV-G-ΔH108R showed a delayed replication in swine macrophage cultures. A group of five pigs, intramuscularly inoculated with 10 HAD of ASFV-G-ΔH108R, was observed over a 28-day period and compared with a similar group of animals inoculated with similar doses of the parental virulent virus. While all animals inoculated with ASFV-G developed an acute fatal disease, ASFV-G-ΔH108R inoculated animals, with the exception of one animal showing a protracted but fatal form of the disease, all survived the infection, remaining clinically healthy during the observational period. The surviving animals presented protracted viremias with lower virus titers compared with those of animals inoculated with the parental virus, and all of them developed a strong virus-specific antibody response. Importantly, all animals surviving ASFV-G-ΔAH108R infection were protected when challenged with the virulent parental strain, ASFV-G. This report constitutes the first evidence that the H108R gene is involved in ASFV virulence in swine and that the deletion of this gene may be used as a tool to increase the attenuation of currently experimental vaccines to improve their safety profiles. Currently, there is no commercial vaccine available to prevent ASF. ASFV-Georgia2007 (ASFV-G) and its field isolate derivatives are producing a large pandemic which is drastically affecting pork production in Eurasia. We present here the discovery of a novel virus determinant of virulence, the H108R gene, which, when deleted from the ASFV-G genome, significantly reduces virus virulence in domestic swine. Additionally, animals that survive the inoculation with a recombinant virus harboring a deletion of the H108R gene, ASFV-G-ΔH108R, are protected against a challenge with the virulent parental virus. Although presenting residual virulence, ASFV-G-ΔH108R confers protection even at low doses (10 HAD), demonstrating its potential to be used as an additional gene deletion to increase the safety profile of the preexisting vaccine candidate.
非洲猪瘟病毒（ASFV）是非洲猪瘟（ASF）的病原体，这是一种破坏性疾病，影响家猪和野猪，目前正在引发全球大流行，严重影响了养猪业。在这里，我们证明了从高致病性 ASFV-Georgia2007（ASFV-G）基因组菌株中删除以前未表征的 ASFV 基因 H108R 可降低家猪的毒力。ASFV-G-ΔH108R 是一种缺失 H108R 基因的重组病毒，用于评估 H108R 基因在猪体内的复制和毒力作用。ASFV-G-ΔH108R 在猪巨噬细胞培养物中的复制呈延迟状态。一组 5 头猪，肌肉内接种 10 HAD 的 ASFV-G-ΔH108R，观察 28 天，并与接种类似剂量亲本病毒的类似动物组进行比较。所有接种 ASFV-G 的动物均发生急性致命疾病，而接种 ASFV-G-ΔH108R 的动物除了一头动物表现出延长但致命的疾病形式外，所有动物均存活下来，在观察期间保持临床健康。与接种亲本病毒的动物相比，存活的动物表现出延长的病毒血症和较低的病毒滴度，并且所有动物均产生了强烈的病毒特异性抗体反应。重要的是，所有感染 ASFV-G-ΔAH108R 的动物在受到高致病性亲本株 ASFV-G 的攻击时都得到了保护。本报告首次证明 H108R 基因参与了猪体内 ASFV 的毒力，并且该基因的缺失可用作工具来增加目前实验性疫苗的减毒作用，以提高其安全性。目前，尚无预防 ASF 的商业疫苗。ASFV-Georgia2007（ASFV-G）及其田间分离株衍生物正在引发一场大规模的大流行，严重影响了欧亚大陆的猪肉生产。在这里，我们发现了一种新的病毒毒力决定因素，即 H108R 基因，当从 ASFV-G 基因组中删除时，该基因可显著降低家猪体内的病毒毒力。此外，感染携带 H108R 基因缺失的重组病毒 ASFV-G-ΔH108R 的动物在受到亲代病毒的攻击时会受到保护。尽管仍具有残余毒力，但 ASFV-G-ΔH108R 甚至在低剂量（10 HAD）下也能提供保护，表明其有潜力用作增加现有候选疫苗安全性的另一个基因缺失。
