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非洲猪瘟病毒 MGF-110-9L 缺失突变体能使病毒在猪体内的毒力减弱。

African Swine Fever Virus MGF-110-9L-deficient Mutant Has Attenuated Virulence in Pigs.

机构信息

State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.

出版信息

Virol Sin. 2021 Apr;36(2):187-195. doi: 10.1007/s12250-021-00350-6. Epub 2021 Mar 10.

Abstract

African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), an often lethal disease in domestic and wild pigs. ASF represents a major threat to the swine industry worldwide. Currently, no commercial vaccine is available because of the complexity of ASFV or biosecurity concerns. Live attenuated viruses that are naturally isolated or genetically manipulated have demonstrated reliable protection against homologous ASFV strain challenge. In the present study, a mutant ASFV strain with the deletion of ASFV MGF-110-9L (ASFV-Δ9L) was generated from a highly virulent ASFV CN/GS/2018 parental strain, a genotype II ASFV. Relative to the parental ASFV isolate, deletion of the MGF-110-9L gene significantly decreased the ability of ASFV-Δ9L to replicate in vitro in primary swine macrophage cell cultures. The majority of animals inoculated intramuscularly with a low dose of ASFV-Δ9L (10 HAD) remained clinically normal during the 21-day observational period. Three of five ASFV-Δ9L-infected animals displayed low viremia titers and low virus shedding and developed a strong virus-specific antibody response, indicating partial attenuation of the ASFV-Δ9L strain in pigs. The findings imply the potential usefulness of the ASFV-Δ9L strain for further development of ASF control measures.

摘要

非洲猪瘟病毒(ASFV)是非洲猪瘟(ASF)的病原体,ASF 是家猪和野猪的一种常发性致命疾病。ASF 是目前全球养猪业面临的主要威胁。由于 ASFV 的复杂性或生物安全问题,目前尚无商业疫苗可用。自然分离或基因改造的减毒活病毒已被证明能可靠地抵抗同源 ASFV 株的挑战。在本研究中,从一株高致病性 ASFV CN/GS/2018 亲本株(基因型 II ASFV)中生成了缺失 ASFV MGF-110-9L(ASFV-Δ9L)的突变 ASFV 株。与亲本 ASFV 分离株相比,缺失 MGF-110-9L 基因显著降低了 ASFV-Δ9L 在原代猪巨噬细胞培养物中体外复制的能力。在 21 天的观察期内,肌肉注射低剂量 ASFV-Δ9L(10 HAD)的大多数动物在临床上保持正常。5 只 ASFV-Δ9L 感染动物中有 3 只表现出低病毒血症滴度和低病毒脱落,并产生强烈的病毒特异性抗体反应,表明 ASFV-Δ9L 株在猪中部分减毒。这些发现表明 ASFV-Δ9L 株在进一步开发 ASF 控制措施方面具有潜在的应用价值。

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