Evolution of H9N2 avian influenza virus in embryonated chicken eggs with or without homologous vaccine antibodies.
Evolution of H9N2 avian influenza virus in embryonated chicken eggs with or without homologous vaccine antibodies.
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H9N2禽流感病毒在含或不含同源疫苗抗体的鸡胚中的进化
DOI：
10.1186/s12917-018-1391-6
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发表时间：
2018-03-06
影响因子：
2.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Jin H;Wang W;Yang X;Su H;Fan J;Zhu R;Wang S;Shi H;Liu X
疫苗构成了一种不同于自然选择的独特选择压力，驱动着流感病毒的进化。在这项研究中，A/Chicken/Shanghai/F/1998 (H9N2) 在特定的无病原体的胚胎鸡蛋中持续传代，有或没有来自同源母体抗体诱导的抗体的选择压力。评估了传代病毒的基因突变、抗原漂移、复制和致病性。传代病毒的抗原漂移发生在抗体选择压力下的第 47 代 (vF47) 和没有抗体选择压力的第 52 代 (nF52) 中。 vF47病毒中观察到7个突变，其中PB2中3个，HA中4个；而nF52病毒中观察到12个突变，其中PB2中3个，PB1中2个，HA中4个，NP中1个，NA中1个，NS中1个。值得注意的是，vF47 病毒的 HA 片段序列与 nF52 病毒的 HA 片段序列 100% 同源。与亲本病毒F/98相比，vF47和nF52病毒均表现出增强的复制，但nF52比vF47表现出更高水平的复制和致病性。源自亲代病毒F/98的无活性疫苗不能提供针对vF47或nF52病毒攻击的保护，但源自vF47或nF52病毒的无活性疫苗能够针对使用F/98的攻击提供保护。总而言之，在有或没有同源母体抗体诱导的抗体选择性压力的情况下，H9N2病毒的传代表现出遗传变异、复制增强和变异抗原性。抗体的选择压力似乎在鸡蛋模型中的抗原漂移中不起关键作用，但可能会影响 H9N2 病毒的遗传变异和复制能力。这些结果增进了对 H9N2 流感病毒进化的了解，并可能有助于选择合适的疫苗种子。
Vaccines constitute a unique selective pressure, different from natural selection, drives the evolution of influenza virus. In this study, A/Chicken/Shanghai/F/1998 (H9N2) was continually passaged in specific pathogen-free embryonated chicken eggs with or without selective pressures from antibodies induced by homologous maternal antibodies. Genetic mutations, antigenic drift, replication, and pathogenicity of the passaged virus were evaluated. Antigenic drift of the passaged viruses occurred in the 47th generation (vF47) under selective pressure on antibodies and in the 52nd generation (nF52) without selective pressure from antibodies. Seven mutations were observed in the vF47 virus, with three in PB2 and four in HA, whereas 12 mutations occurred in the nF52 virus, with three in PB2, two in PB1, four in HA, one in NP, one in NA, and one in NS. Remarkably, the sequences of the HA segment from vF47 were 100% homologous with those of the nF52 virus. Both the vF47 and nF52 viruses showed enhanced replication compared to the parental virus F/98, but higher levels of replication and pathogenicity were displayed by nF52 than by vF47. An inactive vaccine derived from the parental virus F/98 did not confer protection against challenges by either the vF47 or nF52 virus, but inactive vaccines derived from the vF47 or nF52 virus were able to provide protection against a challenge using F/98. Taken together, the passage of H9N2 viruses with or without selective pressure of the antibodies induced by homologous maternal antibodies showed genetic variation, enhanced replication, and variant antigenicity. Selective pressure of the antibody does not seem to play a key role in antigenic drift in the egg model but may impact the genetic variation and replication ability of H9N2 viruses. These results improve understanding of the evolution of the H9N2 influenza virus and may aid in selecting appropriate vaccine seeds.
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