关键词: Muscovy duck parvovirus goose parvovirus rMDPV recombination rescue virulence

Mesh : Animals Ducks Virulence Parvoviridae Infections / virology veterinary Poultry Diseases / virology Capsid Proteins / genetics Recombination, Genetic Point Mutation Parvovirinae / genetics pathogenicity

来  源:   DOI:10.1080/21505594.2024.2366874   PDF(Pubmed)

Abstract:
Recombinant Muscovy duck parvovirus (rMDPV) is a product of genetic recombination between classical Muscovy duck parvovirus (MDPV) and goose parvovirus (GPV). The recombination event took place within a 1.1-kb DNA segment located in the middle of the VP3 gene, and a 187-bp sequence extending from the P9 promoter to the 5\' initiation region of the Rep1 ORF. This resulted in the alteration of five amino acids within VP3. Despite these genetic changes, the precise influence of recombination and amino acid mutations on the pathogenicity of rMDPV remains ambiguous. In this study, based on the rMDPV strain ZW and the classical MDPV strain YY, three chimeric viruses (rZW-mP9, rZW-mPR187, and rYY-rVP3) and the five amino acid mutations-introduced mutants (rZW-g5aa and rYY-5aa(ZW)) were generated using reverse genetic technology. When compared to the parental virus rZW, rZW-g5aa exhibited a prolonged mean death time (MDT) and a decreased median lethal dose (ELD50) in embryonated duck eggs. In contrast, rYY-5aa(ZW) did not display significant differences in MDT and ELD50 compared to rYY. In 2-day-old Muscovy ducklings, infection with rZW-g5aa and rYY-5aa(ZW) resulted in mortality rates of only 20% and 10%, respectively, while infections with the three chimeric viruses (rZW-mP9, rZW-mPR187, rYY-rVP3) and rZW still led to 100% mortality. Notably, rYY-rVP3, containing the VP3 region from strain ZW, exhibited 50% mortality in 6-day-old Muscovy ducklings and demonstrated significant horizontal transmission. Collectively, our findings indicate that recombination and consequent amino acid changes in VP3 have a synergistic impact on the heightened virulence of rMDPV in Muscovy ducklings.
摘要:
重组番鸭细小病毒(rMDPV)是经典番鸭细小病毒(MDPV)和鹅细小病毒(GPV)之间遗传重组的产物。重组事件发生在位于VP3基因中间的1.1kbDNA片段中,和从P9启动子延伸到Rep1ORF的5'起始区的187bp序列。这导致VP3内五个氨基酸的改变。尽管有这些基因变化,重组和氨基酸突变对rMDPV致病性的确切影响仍然不明确.在这项研究中,基于rMDPV菌株ZW和经典MDPV菌株YY,使用反向遗传技术产生了三种嵌合病毒(rZW-mP9,rZW-mPR187和rYY-rVP3)和五个引入氨基酸突变的突变体(rZW-g5aa和rYY-5aa(ZW))。与亲本病毒rZW相比,rZW-g5aa在含胚鸭蛋中表现出延长的平均死亡时间(MDT)和降低的中位致死剂量(ELD50)。相比之下,与rYY相比,rYY-5aa(ZW)在MDT和ELD50方面没有显着差异。在2日龄的番鸭身上,感染rZW-g5aa和rYY-5aa(ZW)导致的死亡率只有20%和10%,分别,而三种嵌合病毒(rZW-mP9,rZW-mPR187,rYY-rVP3)和rZW的感染仍导致100%的死亡率。值得注意的是,rYY-rVP3,包含来自菌株ZW的VP3区域,6日龄番鸭的死亡率为50%,并表现出明显的水平传播。总的来说,我们的发现表明,VP3中的重组和随之而来的氨基酸变化对番鸭rMDPV的毒力增强具有协同影响。
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