Ou Xumin, Mao Sai, Cao Jingyu, Cheng Anchun, Wang Mingshu, Zhu Dekang, Chen Shun, Jia Renyong, Liu Mafeng, Sun Kunfeng, Yang Qiao, Wu Ying, Chen Xiaoyue
Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, People's Republic of China.
Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, Chengdu City, Sichuan, People's Republic of China.
PLoS One. 2017 Jun 14;12(6):e0178993. doi: 10.1371/journal.pone.0178993. eCollection 2017.
Because of their better immunogenicity and the improved protection they afford, live attenuated vaccines derived from serial passaging in an abnormal host are widely used to protect humans or animals from certain pathogens. Here, we used a virulent and a chicken embryo-attenuated duck hepatitis A virus genotype 1 to compare the different regulated immune responses induced by viruses with differing virulence. In this study, the attenuated strains had lower protein expression levels than the virulent strains as identified by immunohistochemistry. This may be caused by apparent codon usage bias selected during passage. Furthermore, lower translation efficiency led to decreased viral replication, which is highly dependent on non-structural viral protein expression. Although the two strains had differing levels of virulence, both could induce strong innate immune responses and robust Tc or Th cell populations during the early stages of the immune response. However, due to fixed single nucleotide polymorphisms (SNPs) selected by passage, the virulent and attenuated strains may induce differing immune responses, with stronger Tc cell immunity induced by the attenuated strain in the spleen and thymus and stronger Tc cell immunity induced by the virulent strain in the liver, lung, bursa of Fabricius and Harderian gland. Four immune related genes (RIG-1, MDA5, IFN-β, and IL-6) were highly differentially expressed in the Harderian gland, bursa of Fabricius and thymus. This study has provided further information about differences in virus-host interactions between duck hepatitis A viruses of differing virulence.
由于其更好的免疫原性以及所提供的增强保护作用，通过在异常宿主中连续传代获得的减毒活疫苗被广泛用于保护人类或动物免受某些病原体的侵害。在此，我们使用了一种强毒株和一种鸡胚减毒的1型鸭甲型肝炎病毒来比较不同毒力的病毒所诱导的不同调节免疫反应。在本研究中，通过免疫组织化学鉴定，减毒株的蛋白质表达水平低于强毒株。这可能是由于传代过程中选择的明显密码子使用偏好所致。此外，较低的翻译效率导致病毒复制减少，而病毒复制高度依赖于非结构病毒蛋白的表达。尽管这两种毒株的毒力水平不同，但在免疫反应的早期阶段，它们都能诱导强烈的先天免疫反应以及强大的Tc或Th细胞群体。然而，由于传代选择的固定单核苷酸多态性（SNP），强毒株和减毒株可能诱导不同的免疫反应，减毒株在脾脏和胸腺中诱导更强的Tc细胞免疫，而强毒株在肝脏、肺、法氏囊和哈德氏腺中诱导更强的Tc细胞免疫。四个免疫相关基因（RIG-1、MDA5、IFN-β和IL-6）在哈德氏腺、法氏囊和胸腺中高度差异表达。本研究提供了关于不同毒力的鸭甲型肝炎病毒之间病毒-宿主相互作用差异的进一步信息。
