Jin Haiyun, Wang Wan, Yang Xueqin, Su Hailong, Fan Jiawen, Zhu Rui, Wang Shifeng, Shi Huoying, Liu Xiufan
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, People's Republic of China.
Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China.
BMC Vet Res. 2018 Mar 6;14(1):71. doi: 10.1186/s12917-018-1391-6.
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.
疫苗构成了一种独特的选择压力，不同于自然选择，它驱动流感病毒的进化。在本研究中，A/鸡/上海/F/1998（H9N2）在无特定病原体的鸡胚中连续传代，传代过程中存在或不存在同源母源抗体诱导的抗体所产生的选择压力。对传代病毒的基因突变、抗原漂移、复制和致病性进行了评估。
传代病毒在抗体选择压力下于第47代（vF47）出现抗原漂移，在无抗体选择压力下于第52代（nF52）出现抗原漂移。在vF47病毒中观察到7个突变，其中PB2有3个，HA有4个；而在nF52病毒中出现12个突变，其中PB2有3个，PB1有2个，HA有4个，NP有1个，NA有1个，NS有1个。值得注意的是，vF47的HA片段序列与nF52病毒的序列100%同源。与亲代病毒F/98相比，vF47和nF52病毒的复制均增强，但nF52的复制水平和致病性高于vF47。源自亲代病毒F/98的灭活疫苗不能对vF47或nF52病毒的攻击提供保护，但源自vF47或nF52病毒的灭活疫苗能够对使用F/98进行的攻击提供保护。
总体而言，H9N2病毒在有或无同源母源抗体诱导的抗体选择压力下传代均表现出基因变异、复制增强和抗原性变异。抗体的选择压力在卵模型的抗原漂移中似乎不发挥关键作用，但可能影响H9N2病毒的基因变异和复制能力。这些结果增进了对H9N2流感病毒进化的理解，并可能有助于选择合适的疫苗种子株。
