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MGF 110-11L基因在非洲猪瘟病毒复制及毒力中的作用

Involvement of the MGF 110-11L Gene in the African Swine Fever Replication and Virulence.

作者信息

Tamás Vivien, Righi Cecilia, Mészáros István, D'Errico Federica, Olasz Ferenc, Casciari Cristina, Zádori Zoltán, Magyar Tibor, Petrini Stefano, Feliziani Francesco

机构信息

Institute for Veterinary Medical Research, Hungária krt. 21, 1143 Budapest, Hungary.

Istituto Zooprofilattico Sperimentale Umbria-Marche "Togo Rosati", Via Gaetano Salvemini, 1, 06126 Perugia, Italy.

出版信息

Vaccines (Basel). 2023 Apr 14;11(4):846. doi: 10.3390/vaccines11040846.

Abstract

African swine fever (ASF) is a highly lethal hemorrhagic viral disease that causes extensive economic and animal welfare losses in the Eurasian pig () population. To date, no effective and safe vaccines have been marketed against ASF. A starting point for vaccine development is using naturally occurring attenuated strains as a vaccine base. Here, we aimed to remove the multigene family (MGF) 110 gene of unknown function from the Lv17/WB/Rie1 genome to improve the usability of the virus as a live-attenuated vaccine, reducing unwanted side effects. The MGF 110-11L gene was deleted using the CRISPR/Cas9 method, and the safety and efficacy of the virus were tested in pigs after isolation. The vaccine candidates administered at high doses showed reduced pathogenicity compared to the parental strain and induced immunity in vaccinated animals, although several mild clinical signs were observed. Although Lv17/WB/Rie1/d110-11L cannot be used as a vaccine in its current form, it was encouraging that the undesirable side effects of Lv17/WB/Rie1 at high doses can be reduced by additional mutations without a significant reduction in its protective capacity.

摘要

非洲猪瘟(ASF)是一种高致死性出血性病毒性疾病,在欧亚猪群中造成广泛的经济损失和动物福利损失。迄今为止,尚无针对ASF的有效且安全的疫苗上市。疫苗研发的一个起点是使用自然发生的减毒株作为疫苗基础。在此,我们旨在从Lv17/WB/Rie1基因组中去除功能未知的多基因家族(MGF)110基因,以提高该病毒作为减毒活疫苗的可用性,减少不必要的副作用。使用CRISPR/Cas9方法删除了MGF 110-11L基因,并在分离后对猪进行了病毒安全性和有效性测试。与亲本毒株相比,高剂量接种的候选疫苗致病性降低,且在接种动物中诱导了免疫,尽管观察到了一些轻微的临床症状。虽然Lv17/WB/Rie1/d110-11L目前不能作为疫苗使用,但令人鼓舞的是,通过额外的突变可以减少Lv17/WB/Rie1高剂量时的不良副作用,而其保护能力不会显著降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e035/10145817/c045a301d8b2/vaccines-11-00846-g001.jpg

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