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马立克氏病病毒跨物种传播风险评估

摘  要

马立克氏病病毒作为禽类重要病原体,其跨物种传播风险日益引起学界关注。本研究旨在系统评估MDV的跨物种传播潜力及其潜在公共卫生影响。通过整合流行病学调查、分子进化分析和体外感染实验等多学科方法,对MDV的宿主范围、遗传变异特征及跨种屏障机制进行了全面研究。研究收集了2015-2022年间来自不同地理区域的MDV分离株,采用全基因组测序技术构建系统发育树,并结合受体结合特性分析揭示病毒进化规律。同时,通过建立体外细胞感染模型,评估了MDV对不同哺乳动物细胞的感染能力。结果表明,MDV在进化过程中呈现出显著的适应性突变特征,特别是在囊膜糖蛋白区域检测到多个与宿主范围扩展相关的关键氨基酸位点变异。体外实验证实部分MDV分离株能够有效感染人源细胞系,且表现出持续复制能力。基于生物信息学预测和实验验证,研究首次发现MDV可能利用保守的神经生长因子受体作为跨物种感染的潜在受体。这些发现为理解MDV的跨物种传播机制提供了新的视角,同时也提示需要加强对该病毒的监测和防控措施。本研究不仅填补了MDV跨物种传播风险评估领域的空白,还为制定相关生物安全策略提供了重要的科学依据。

关键词:马立克氏病病毒,跨物种传播,宿主范围,神经生长因子受体


Abstract

Marek's disease virus (MArek's Disease virus) is an important pathogen in poultry, and its risk of cross-species transmission has attracted increasing attention. The aim of this study was to systematically assess the cross-species transmission potential of MDV and its potential public health impact. The host range, genetic variation and cross-species barrier mechanism of MDV were comprehensively studied by integrating epidemiological investigation, molecular evolution analysis and in vitro infection experiments. The study collected MDV isolates from different geographic regions from 2015 to 2022, used whole genome sequencing technology to build phylogenetic trees, and combined with receptor binding characteristics analysis to reveal the evolution of the virus. At the same time, the ability of MDV to infect different mammalian cells was evaluated by establishing in vitro cell infection model. The results showed that MDV showed significant adaptive mutation characteristics during evolution, especially in the glycoprotein region of the capsule, several key amino acid site variants were detected in relation to host range extension. In vitro experiments showed that some MDV isolates could effectively infect human cell lines and showed the ability of sustained replication. Based on bioinformatics predictions and experimental validation, the study shows for the first time that MDV may utilize conserved nerve growth factor receptors as potential receptors for cross-species infections. These findings provide new insights into the mechanisms of cross-species transmission of MDV and suggest the need to strengthen surveillance and control measures against the virus. This study not only fills the gap in the field of risk assessment of cross-species transmission of MDV, but also provides an important scientific basis for formulating relevant biosafety strategies.

Key words: Marek's disease virus, cross-species transmission, host range, nerve growth factor receptor


目  录

1 绪论 1

1.1 马立克氏病病毒跨物种传播研究背景 1

1.2 跨物种传播风险评估的研究意义 1

2 马立克氏病病毒生物学特性分析 1

2.1 病毒基因组结构与功能特征 2

2.2 病毒宿主范围与感染机制 2

2.3 病毒变异与进化特征分析 3

2.4 病毒环境适应性研究 3

3 马立克氏病病毒跨物种传播机制研究 4

3.1 跨物种传播的分子基础 4

3.2 潜在宿主识别与受体分析 5

3.3 种间屏障突破机制探讨 5

3.4 传播途径与环境影响因素 6

4 马立克氏病病毒跨物种传播风险评估模型构建 7

4.1 风险评估指标体系建立 7

4.2 风险因子权重分析方法 7

4.3 定量评估模型构建与验证 8

4.4 风险等级划分与管理建议 9

5 结论 9

参考文献 11

致谢 12

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