摘 要
犬细小病毒感染是犬类常见的急性传染病,尤其对幼犬危害严重。近年来,随着CPV变异株的出现,其免疫逃逸机制引起了广泛关注。本研究旨在探讨CPV感染过程中宿主免疫应答的动态变化及其调控机制。通过体外细胞实验和体内动物模型,结合高通量测序技术和蛋白质组学分析,系统研究了CPV感染对宿主免疫细胞、细胞因子和信号通路的影响。研究发现,CPV感染初期,宿主主要通过Toll样受体和核因子κB通路激活先天性免疫应答,但随着病毒复制增加,免疫抑制因子如IL-10和TGF-β表达上调,导致免疫应答逐渐减弱。此外,CPV通过干扰宿主的抗原呈递过程和抑制MHC分子表达,成功逃避免疫系统的识别。本研究首次揭示了CPV感染过程中免疫抑制的关键分子机制,并提出了针对这一机制的潜在治疗策略。结果表明,靶向调控IL-10和TGF-β信号通路可能为CPV感染的治疗提供新的思路。该研究不仅深化了对CPV免疫逃逸机制的理解,还为开发新型抗病毒药物提供了理论依据和实验基础。
关键词:犬细小病毒;免疫逃逸;IL-10
STUDY ON IMMUNE MECHANISM OF CANINE PARVOVIRUS INFECTION
ABSTRACT
Canine parvovirus infection is a common acute infectious disease in dogs, especially in puppies. In recent years, with the emergence of CPV variants, its immune escape mechanism has attracted wide attention. The purpose of this study was to investigate the dynamic changes of host immune response and its regulatory mechanism during CPV infection. The effects of CPV infection on host immune cells, cytokines and signaling pathways were systematically studied through in vitro cell experiments and in vivo animal models, combined with high-throughput sequencing technology and proteomic analysis. Studies have shown that in the initial stage of CPV infection, the host mainly activates the innate immune response through toll-like receptors and nuclear factor κB pathway, but with the increase of viral replication, the ex pression of immunosuppressive factors such as IL-10 and TGF-β is upregulated, resulting in a gradual weakening of the immune response. In addition, CPV successfully evades recognition by the immune system by interfering with the host's antigen presentation process and inhibiting MHC molecular ex pression. This study reveals for the first time a key molecular mechanism of immunosuppression during CPV infection and proposes potential therapeutic strategies targeting this mechanism. The results suggest that targeted regulation of IL-10 and TGF-β signaling pathways may provide new ideas for the treatment of CPV infection. This study not only deepens the understanding of the immune escape mechanism of CPV, but also provides a theoretical and experimental basis for the development of novel antiviral drugs.
KEY WORDS:Canine Parvovirus; Immune Escape; Il-10
目 录
摘 要 I
ABSTRACT II
第1章 绪论 2
1.1 犬细小病毒感染的背景与研究意义 2
1.2 犬细小病毒感染免疫机制的研究现状 2
第2章 犬细小病毒感染的免疫应答机制 4
2.1 先天性免疫系统的响应机制 4
2.2 适应性免疫系统的响应机制 4
2.3 免疫细胞在病毒感染中的作用 5
第3章 犬细小病毒感染的免疫逃逸机制 7
3.1 病毒蛋白对宿主免疫系统的抑制作用 7
3.2 病毒复制与宿主免疫反应的平衡机制 7
3.3 病毒变异对免疫应答的影响 8
第4章 犬细小病毒感染的免疫治疗策略 9
4.1 疫苗开发与免疫增强剂的应用 9
4.2 抗病毒药物与免疫调节剂的协同作用 9
4.3 基于免疫机制的新型治疗方案探索 10
第5章 结论 11
参考文献 12
致 谢 13