更改的原始数据

非洲猪瘟 （ASF） 由非洲猪瘟病毒 （ASFV） 引起，是一种传染性很强的出血性疾病，对全球养猪业造成严重的社会经济影响。尽管为开发有效的控制策略做出了巨大努力，但 缺乏有效的体外模型仍然是一个关键障碍。一个关键挑战在于 ASFV 的趋向性受限;它强烈感染原代猪肺泡巨噬细胞 （PAM），并且在大多数传代细胞系中表现出较差的复制效果，阻碍了机制研究和抗病毒开发。为了解决这一限制，我们对感染早期 ASFV 感染的 PAM （原代细胞） 和 ZMAC-4 细胞 （传代巨噬细胞系） 进行了比较转录组学分析。我们的研究结果揭示了两种细胞类型之间病毒易感性和宿主反应的显着差异。转录组分析确定了关键途径的不同激活： ZMAC-4 细胞主要上调氧化应激相关途径，而 PAMs 表现出强大的细胞因子信号传导和免疫激活。通过敲低和过表达实验对差异表达基因 （DEGs） 的进一步分析表明，junctophilin-4 （JPH4） 和细胞色素 P450 1A1 （CYP1A1） 是两个潜在的宿主限制因子。本研究描述了 ASFV 允许细胞与半允许细胞中的早期宿主病毒动力学，提供了对嗜性的机制见解，并强调 JPH4/CYP1A1 是抗病毒策略的新靶点。这些发现为合理设计抗病毒策略和改进疫苗平台奠定了基础，从而解决了非洲猪瘟研究中的关键空白。

African Swine Fever (ASF), caused by the African Swine Fever Virus (ASFV), is a highly contagious hemorrhagic disease that imposes severe socioeconomic impacts on the global swine industry. Despite substantial efforts to develop effective control strategies, the lack of valid in vitro models remains a critical barrier. A key challenge stems from the restricted tropism of ASFV: it strongly infects primary porcine alveolar macrophages (PAM) but exhibits poor replication efficiency in most passaged cell lines, hindering mechanistic research and antiviral development. To address this limitation, we conducted comparative transcriptomic analysis on ASFV-infected PAM (primary cells) and ZMAC-4 cells (passaged macrophage cell line) at the early stage of infection. Our findings revealed significant differences in viral susceptibility and host responses between the two cell types. Transcriptomic analysis identified differential activation of key pathways: ZMAC-4 cells primarily upregulated oxidative stress-related pathways, while PAMs showed robust cytokine signaling and immune activation. Further analysis of differentially expressed genes (DEGs) via knockdown and overexpression experiments indicated that junctophilin-4 (JPH4) and cytochrome P450 1A1 (CYP1A1) are potential host restriction factors. This study delineates early host-virus dynamics in ASFV-permissive and semi-permissive cells, provides mechanistic insights into tropism, and highlights JPH4/CYP1A1 as novel targets for antiviral strategies. These findings lay the foundation for rational design of antiviral strategies and improvement of vaccine platforms, thereby filling key gaps in ASF research.