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基因缺失使非洲猪瘟病毒部分减毒。

Deletion of the Gene in African Swine Fever Virus Partially Reduces Virus Virulence in Swine.

机构信息

Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA.

Oak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USA.

出版信息

Viruses. 2023 Jun 29;15(7):1477. doi: 10.3390/v15071477.

Abstract

African swine fever (ASF) is a highly contagious disease that affects wild and domestic swine. Currently, the disease is present as a pandemic affecting pork production in Eurasia and the Caribbean region. The etiological agent of ASF is a large, highly complex structural virus (ASFV) harboring a double-stranded genome encoding for more than 160 proteins whose functions, in most cases, have not been experimentally characterized. We show here that deletion of the ASFV gene from the genome of the highly virulent ASFV-Georgia2010 (ASFV-G) isolate partially decreases virus virulence when experimentally inoculated in domestic swine. ASFV-G-∆H240R, a recombinant virus harboring the deletion of the gene, was produced to evaluate the function of the gene in the development of disease in pigs. While all animals intramuscularly inoculated with 10 HAD of ASFV-G developed a fatal form of the disease, forty percent of pigs receiving a similar dose of ASFV-G-∆H240R survived the infection, remaining healthy during the 28-day observational period, and the remaining sixty percent developed a protracted but fatal form of the disease compared to that induced by ASFV-G. Additionally, all animals inoculated with ASFV-G-∆H240R presented protracted viremias with reduced virus titers when compared with those found in animals inoculated with ASFV-G. Animals surviving infection with ASFV-G-∆H240R developed a strong virus-specific antibody response and were protected against the challenge of the virulent parental ASFV-G.

摘要

非洲猪瘟(ASF)是一种高度传染性疾病,会影响野生和家养猪。目前,该疾病在欧亚大陆和加勒比地区呈大流行趋势,严重影响猪肉生产。ASF 的病原体是一种大型、高度复杂的结构病毒(ASFV),其双链基因组编码超过 160 种蛋白质,其中大多数蛋白质的功能尚未通过实验进行表征。我们在此表明,从高度致命的 ASFV-Georgia2010(ASFV-G)分离株的基因组中删除 ASFV 基因 会部分降低病毒在实验接种的家猪中的毒力。ASFV-G-∆H240R 是一种携带 基因缺失的重组病毒,用于评估该基因在猪疾病发展中的功能。虽然所有肌肉内接种 10 HAD 的 ASFV-G 的动物都发展为致命形式的疾病,但接受类似剂量的 ASFV-G-∆H240R 的 40%的猪幸存下来,在 28 天的观察期内保持健康,而其余 60%的猪发展为比 ASFV-G 诱导的疾病更迁延但致命的形式。此外,与接种 ASFV-G 的动物相比,所有接种 ASFV-G-∆H240R 的动物的病毒血症持续时间延长,病毒滴度降低。感染 ASFV-G-∆H240R 的动物产生了强烈的病毒特异性抗体反应,并对致命的亲本 ASFV-G 的挑战具有保护作用。

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