NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China.
Animal Model Exp Med. 2024 Oct;7(5):717-731. doi: 10.1002/ame2.12415. Epub 2024 May 15.
Hand, foot and mouth disease (HFMD) is a common infectious disease caused by viral infection by a variety of enteroviruses, with coxsackievirus A 10 (CA10) having become more prevalent in recent years.
In this study, models of CA10 infection were established in 7-day-old Institute of Cancer Research (ICR) mice by intraperitoneal injection to analyze the pathogenicity of the virus. RNA sequencing analysis was used to screen the differentially expressed genes (DEGs) after CA10 infection. Coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) infections were also compared with CA10.
After CA10 virus infection, the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection. We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle. The RNA-sequencing analysis showed that the DEGs in blood, muscle, thymus and spleen showed heterogeneity after CA10 infection and the most up-regulated DEGs in muscle were enriched in immune-related pathways. Compared with CA16 and EV71 infection, CA10 may have an inhibitory effect on T helper (Th) cell differentiation and cell growth. Additionally, the common DEGs in the three viruses were most enriched in the immune system response, including the Toll-like receptor pathway and the nucleotide-binding and oligomerization domain (NOD)-like pathway.
Our findings revealed a group of genes that coordinate in response to CA10 infection, which increases our understanding of the pathological mechanism of HFMD.
手足口病（HFMD）是一种常见的传染病，由多种肠道病毒引起的病毒感染引起，近年来柯萨奇病毒 A10（CA10）变得更为普遍。
本研究通过腹腔注射建立 7 日龄 ICR 小鼠 CA10 感染模型，分析病毒的致病性。采用 RNA 测序分析筛选 CA10 感染后的差异表达基因（DEGs）。还比较了 CA16 和 EV71 与 CA10 的感染。
CA10 病毒感染后，感染后 3 天小鼠出现后肢瘫痪，感染后 5 天体重减轻。我们观察到病毒在各种组织中的复制和骨骼肌中严重的炎症细胞浸润。RNA 测序分析显示，CA10 感染后血液、肌肉、胸腺和脾脏中的 DEGs 表现出异质性，肌肉中上调最明显的 DEGs 富集在免疫相关途径中。与 CA16 和 EV71 感染相比，CA10 可能对辅助性 T（Th）细胞分化和细胞生长有抑制作用。此外，三种病毒中常见的 DEGs 最富集于免疫系统反应，包括 Toll 样受体途径和核苷酸结合和寡聚化结构域（NOD）样途径。
我们的研究结果揭示了一组协调应对 CA10 感染的基因，增加了我们对手足口病病理机制的理解。
