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从格鲁吉亚分离株中删除非洲猪瘟病毒组蛋白样蛋白 A104R 可极大降低病毒在家猪中的毒力。

Deletion of African Swine Fever Virus Histone-like Protein, A104R from the Georgia Isolate Drastically Reduces Virus Virulence in Domestic Pigs.

机构信息

Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture Greenport, Greenport, NY 11944, USA.

Department of Pathobiology and Population Medicine, Mississippi State University, P.O. Box 6100, Starkville, MS 39762, USA.

出版信息

Viruses. 2022 May 22;14(5):1112. doi: 10.3390/v14051112.

DOI:10.3390/v14051112
PMID:35632853
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9146580/
Abstract

African swine fever virus (ASFV) is the etiological agent of a frequently lethal disease, ASF, affecting domestic and wild swine. Currently, ASF is causing a pandemic affecting pig production in Eurasia. There are no vaccines available, and therefore control of the disease is based on culling infected animals. We report here that deletion of the ASFV gene A104R, a virus histone-like protein, from the genome of the highly virulent ASFV-Georgia2010 (ASFV-G) strain induces a clear decrease in virus virulence when experimentally inoculated in domestic swine. A recombinant virus lacking the A104R gene, ASFV-G-∆A104R, was developed to assess the role of the A104R gene in disease production in swine. Domestic pigs were intramuscularly inoculated with 10 HAD of ASFV-G-∆A104R, and compared with animals that received a similar dose of virulent ASFV-G. While all ASFV-G inoculated animals developed a fatal form of the disease, animals receiving ASFV-G-∆A104R survived the challenge, remaining healthy during the 28-day observational period, with the exception of only one showing a protracted but fatal form of the disease. ASFV-G-∆A104R surviving animals presented protracted viremias with reduced virus titers when compared with those found in animals inoculated with ASFV-G, and all of them developed a strong virus-specific antibody response. This is the first report demonstrating that the A104R gene is involved in ASFV virulence in domestic swine, suggesting that A104R deletion may be used to increase the safety profile of currently experimental vaccines.

摘要

非洲猪瘟病毒(ASFV)是一种经常致命的疾病——非洲猪瘟(ASF)的病原体,影响家猪和野猪。目前,ASF 正在引发一场影响欧亚大陆养猪业的大流行。目前尚无可用的疫苗,因此疾病的控制基于扑杀感染动物。我们在此报告,从高致病性 ASFV-Georgia2010(ASFV-G)株的基因组中删除病毒组蛋白样蛋白 A104R 基因,当在实验中接种家猪时,可明显降低病毒的毒力。为了评估 A104R 基因在猪中产生疾病的作用,我们开发了一种缺失 A104R 基因的重组病毒,ASFV-G-∆A104R。将 10 HAD 的 ASFV-G-∆A104R 肌肉内接种家猪,并与接受类似剂量强毒 ASFV-G 的动物进行比较。所有接受 ASFV-G 接种的动物均发展为致命形式的疾病,而接受 ASFV-G-∆A104R 接种的动物则存活下来,在 28 天的观察期内保持健康,只有一只动物表现出延长但致命的疾病形式。与接受 ASFV-G 接种的动物相比,存活的 ASFV-G-∆A104R 动物的病毒血症持续时间较长,病毒滴度降低,并且所有动物均产生强烈的病毒特异性抗体反应。这是第一个证明 A104R 基因参与家猪 ASFV 毒力的报告,表明 A104R 缺失可能用于提高当前实验疫苗的安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/1083c754946b/viruses-14-01112-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/9e68f1142885/viruses-14-01112-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/1083c754946b/viruses-14-01112-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/5e94dd0b0ef8/viruses-14-01112-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/6ec5bbde96ec/viruses-14-01112-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/318c544fe0d8/viruses-14-01112-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/c3432f53366a/viruses-14-01112-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/9e68f1142885/viruses-14-01112-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9f6/9146580/1083c754946b/viruses-14-01112-g007.jpg

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