Academician Workstation, Changchun University of Chinese Medicine, Changchun, China.
College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
Front Immunol. 2021 Nov 18;12:781718. doi: 10.3389/fimmu.2021.781718. eCollection 2021.
Norovirus (NoV) is a zoonotic virus that causes diarrhea in humans and animals. Outbreaks in nosocomial settings occur annually worldwide, endangering public health and causing serious social and economic burdens. The latter quarter of 2016 witnessed the emergence of the GII.P16-GII.2 recombinant norovirus throughout Asia. This genotype exhibits strong infectivity and replication characteristics, proposing its potential to initiate a pandemic. There is no vaccine against GII.P16-GII.2 recombinant norovirus, so it is necessary to design a preventive vaccine. In this study, GII.P16-GII.2 type norovirus virus-like particles (VLPs) were constructed using the baculovirus expression system and used to conduct immunizations in mice. After immunization of mice, mice were induced to produce memory T cells and specific antibodies, indicating that the VLPs induced specific cellular and humoral immune responses. Further experiments were then initiated to understand the underlying mechanisms involved in antigen presentation. Towards this, we established co-cultures between dendritic cells (DCs) or macrophages (Mø) and naïve CD4+T cells and simulated the antigen presentation process by incubation with VLPs. Thereafter, we detected changes in cell surface molecules, cytokines and related proteins. The results indicated that VLPs effectively promoted the phenotypic maturation of Mø but not DCs, as indicated by significant changes in the expression of MHC-II, costimulatory factors and related cytokines in Mø. Moreover, we found VLPs caused Mø to polarize to the M1 type and release inflammatory cytokines, thereby inducing naïve CD4+ T cells to perform Th1 immune responses. Therefore, this study reveals the mechanism of antigen presentation involving GII.P16-GII.2 recombinant norovirus VLPs, providing a theoretical basis for both understanding responses to norovirus infection as well as opportunities for vaccine development.
诺如病毒（NoV）是一种人畜共患病毒，可导致人类和动物腹泻。全球每年都有医院感染暴发，危及公众健康并造成严重的社会和经济负担。2016 年第四季度，亚洲出现了 GII.P16-GII.2 重组诺如病毒。这种基因型具有很强的感染性和复制特性，表明其有引发大流行的潜力。目前尚无针对 GII.P16-GII.2 重组诺如病毒的疫苗，因此需要设计预防性疫苗。在本研究中，使用杆状病毒表达系统构建了 GII.P16-GII.2 型诺如病毒病毒样颗粒（VLPs），并用于小鼠免疫接种。免疫接种后，诱导小鼠产生记忆 T 细胞和特异性抗体，表明 VLPs 诱导了特异性细胞和体液免疫反应。然后进一步开展实验以了解抗原呈递涉及的潜在机制。为此，我们建立了树突状细胞（DC）或巨噬细胞（Mø）与幼稚 CD4+T 细胞的共培养物，并通过与 VLPs 孵育模拟抗原呈递过程。此后，我们检测了细胞表面分子、细胞因子和相关蛋白的变化。结果表明，VLPs 有效地促进了 Mø 的表型成熟，但对 DC 没有作用，因为 Mø 中 MHC-II、共刺激因子和相关细胞因子的表达发生了显著变化。此外，我们发现 VLPs 导致 Mø 向 M1 型极化并释放炎症细胞因子，从而诱导幼稚 CD4+T 细胞产生 Th1 免疫反应。因此，本研究揭示了 GII.P16-GII.2 重组诺如病毒 VLPs 涉及的抗原呈递机制，为理解诺如病毒感染的反应提供了理论依据，并为疫苗开发提供了机会。
