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评估和确定猪用密码子对去优化 PRRSV-1 疫苗候选株的合适传代数。

Evaluation and Determination of a Suitable Passage Number of Codon Pair Deoptimized PRRSV-1 Vaccine Candidate in Pigs.

机构信息

Viral Disease Division, Animal and Plant Quarantine Agency, Gimcheon-si 39660, Republic of Korea.

Department of Animal Veterinary Development, BioPOA, Hwaseong-si 18469, Republic of Korea.

出版信息

Viruses. 2023 Apr 27;15(5):1071. doi: 10.3390/v15051071.

DOI:10.3390/v15051071
PMID:37243157
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10220689/
Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is major economic problem given its effects on swine health and productivity. Therefore, we evaluated the genetic stability of a codon pair de-optimized (CPD) PRRSV, E38-ORF7 CPD, as well as the master seed passage threshold that elicited an effective immune response in pigs against heterologous virus challenge. The genetic stability and immune response of every 10th passage (out of 40) of E38-ORF7 CPD was analyzed through whole genome sequencing and inoculation in 3-week-old pigs. E38-ORF7 CPD passages were limited to 20 based on the full-length mutation analysis and animal test results. After 20 passages, the virus could not induce antibodies to provide effective immunity and mutations accumulated in the gene, which differed from the CPD gene, presenting a reason for low infectivity. Conclusively, the optimal passage number of E38-ORF7 CPD is 20. As a vaccine, this may help overcome the highly diverse PRRSV infection with substantially enhanced genetic stability.

摘要

猪繁殖与呼吸综合征病毒(PRRSV)对猪的健康和生产力有影响,是一个主要的经济问题。因此,我们评估了一种密码子对去优化(CPD)的 PRRSV,E38-ORF7 CPD 的遗传稳定性,以及引发猪对异源病毒攻击产生有效免疫反应的主种子传代阈值。通过对 3 周龄猪进行全基因组测序和接种,分析了 E38-ORF7 CPD 的每 10 次传代(共 40 次)的遗传稳定性和免疫反应。基于全长突变分析和动物试验结果,E38-ORF7 CPD 的传代次数被限制在 20 次以内。20 次传代后,病毒不能诱导产生抗体提供有效免疫,基因中积累了突变,与 CPD 基因不同,这是感染性降低的原因。总之,E38-ORF7 CPD 的最佳传代次数是 20 次。作为一种疫苗,这可能有助于克服高度多样化的 PRRSV 感染,同时显著提高遗传稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d0/10220689/2fd00dd12922/viruses-15-01071-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d0/10220689/7f056edc14a7/viruses-15-01071-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d0/10220689/ee7ebee83d2c/viruses-15-01071-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d0/10220689/2fd00dd12922/viruses-15-01071-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d0/10220689/7f056edc14a7/viruses-15-01071-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d0/10220689/ee7ebee83d2c/viruses-15-01071-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00d0/10220689/2fd00dd12922/viruses-15-01071-g003.jpg

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2
Genetic diversity of porcine reproductive and respiratory syndrome virus and evaluation of three one-step real-time RT-PCR assays in Korea.韩国猪繁殖与呼吸综合征病毒的遗传多样性分析及三种一步法实时 RT-PCR 检测方法的评估。
BMC Vet Res. 2022 Aug 30;18(1):327. doi: 10.1186/s12917-022-03407-0.
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Detection of Multiple Lineages of PRRSV in Breeding and Growing Swine Farms.
在种猪场和生长育肥猪场检测到多种谱系的猪繁殖与呼吸综合征病毒
Front Vet Sci. 2022 Jun 14;9:884733. doi: 10.3389/fvets.2022.884733. eCollection 2022.
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Vaccinia Virus Attenuation by Codon Deoptimization of the A24R Gene for Vaccine Development.痘苗病毒通过 A24R 基因的密码子去优化实现减毒,用于疫苗开发。
Microbiol Spectr. 2022 Jun 29;10(3):e0027222. doi: 10.1128/spectrum.00272-22. Epub 2022 May 18.
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