Amino Acid Mutations in Hemagglutinin-Neuraminidase Enhance the Virulence and Pathogenicity of the Genotype III Newcastle Disease Vaccine Strain After Intravenous Inoculation.
Amino Acid Mutations in Hemagglutinin-Neuraminidase Enhance the Virulence and Pathogenicity of the Genotype III Newcastle Disease Vaccine Strain After Intravenous Inoculation.
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血凝素神经氨酸酶氨基酸突变增强基因Ⅲ型新城疫疫苗株静脉接种后的毒力和致病性
DOI：
10.3389/fvets.2022.890657
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发表时间：
2022
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
新城疫病毒 (NDV) 是一种通常引起家禽严重疾病的病原体，它持续变异并已进化为 21 种基因型。我们之前分离出一种强效基因型 III NDV JS/7/05/Ch，它是由疫苗株 Mukteswar 进化而来，伴随着血凝素神经氨酸酶 (HN) 的氨基酸突变。在这里，我们试图研究突变 HN 蛋白在 NDV 毒力中的作用。 Mukteswar和JS/7/05/Ch的HN基因通过反向遗传学相互替换，分别产生两种重组病毒rJS/MHN和rMu/JHN。 rMu/JHN将内源性HN蛋白替换为JS/7/05/Ch的HN蛋白，对鸡具有较高的静脉致病性指数(IVPI)值。此外，将双氨基酸突变（JS/7/05/Ch型HN的A494D和E495K）引入Mukteswar的HN蛋白中，产生重组病毒rMukHN494+495JS。该病毒显示出与 rJS/7/05/Ch（通过反向遗传学从亲本 JS/7/05/Ch 产生）相当的 IVPI 值。体外和体内试验进一步表明，HN 中的 A494D 和 E495K 诱导抗原变化、更高的复制水平和更强烈的炎症反应。总而言之，这些发现表明 HN 中的 aa 突变对于静脉注射后基因型 III 新城疫 (ND) 疫苗株的毒力至关重要。我们的研究进一步强调，需要密切监测来监测新城疫疫苗株的遗传变异。
Newcastle disease virus (NDV), the causative agent that generally causes severe disease in poultry, continues to mutate and has thus evolved into 21 genotypes. We previously isolated a velogenic genotype III NDV JS/7/05/Ch that evolved from the vaccine strain Mukteswar, accompanying by amino acid mutations in Hemagglutinin-Neuraminidase (HN). Here, we sought to investigate the role of the mutant HN protein in NDV virulence. The HN genes of Mukteswar and JS/7/05/Ch were replaced reciprocally via reverse genetics, yielding two recombinant viruses rJS/MHN and rMu/JHN, respectively. rMu/JHN, in which the endogenous HN protein was replaced with the HN protein of JS/7/05/Ch, had a higher intravenous pathogenicity index (IVPI) value in chickens. Moreover, dual aa mutations (A494D and E495K from JS/7/05/Ch-type HN) were introduced into the HN protein of Mukteswar to generate the recombinant virus rMukHN494+495JS. This virus showed an equivalent IVPI value to that of rJS/7/05/Ch (generated from parental JS/7/05/Ch via reverse genetics). In vitro and in vivo assays further showed that A494D and E495K in HN induced antigenic changes, a higher replication level and a more intense inflammatory response. Taken together, these findings indicate that aa mutations in HN are crucial for the virulence of the genotype III Newcastle disease (ND) vaccine strain after intravenous inoculation. Our study further highlights that close surveillance is needed to monitor the genetic variation of ND vaccine strains.
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