Zhao Xiaoyang, Zhang Yanyan, Jia Hanying, Lv Lin, Ahsan Md Asif, Fu Xudong, Hu Rongliang, Shen Zhiqiang, Shen Ning
Department of Obstetrics and Gynecology of Sir Run Run Shaw Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
J Virol. 2025 Mar 18;99(3):e0203524. doi: 10.1128/jvi.02035-24. Epub 2025 Feb 11.
African swine fever virus (ASFV) causes epidemics with high mortality; however, effective vaccines and therapies remain missing. Here, we depict a temporal single-cell landscape of primary porcine alveolar macrophages (PAMs) exposed to three different virulent ASFV strains . We found that attenuated and low-virulence ASFV strains tend to exhibit higher viral loads than highly virulent strain, which may result from upregulated RNA polymerase subunit genes expression. On the host side, our study highlights the IRF7-mediated positive feedback loop to the activation of the interferon signaling pathway in cells exposed to attenuated and low virulent ASFV strains. Moreover, we unraveled the PAMs populations marked by expressions of the and , respectively, which produce high levels of interferon-stimulated genes (ISGs) and IL18 to regulate the host response to different virulent ASFV strains. Collectively, our data provide insights into the complex host-virus interactions with various ASFV strain infections, which may shed light on the development of effective antiviral strategies.IMPORTANCEThere is still no available research on the temporal transcriptional profile of host cells exposed to different virulent ASFV strains at the single-cell level. Here, we first profiled the temporal viral and host transcriptomes in PAMs exposed to high virulent, attenuated virulent, and low virulent ASFV strains. Our analysis revealed that attenuated and low-virulence ASFV strains tend to exhibit higher viral loads than highly virulent strains, which may result from upregulated RNA polymerase subunit genes expression. We also found a positive feedback loop of the interferon signaling pathway mediated through IRF7 and identified the populations of PAMs marked by and , respectively, which produce high levels of ISGs and to regulate host response to different virulent ASFV strains. Our study delineated a comprehensive single-cell landscape of host-virus dynamics across ASFV strains with different virulences and would provide an important resource for future research.
非洲猪瘟病毒（ASFV）可引发高死亡率的疫情；然而，目前仍缺乏有效的疫苗和治疗方法。在此，我们描绘了暴露于三种不同强毒力ASFV毒株的原代猪肺泡巨噬细胞（PAM）的单细胞动态图谱。我们发现，与高毒力毒株相比，减毒和低毒力的ASFV毒株往往表现出更高的病毒载量，这可能是由于RNA聚合酶亚基基因表达上调所致。在宿主方面，我们的研究突出了IRF7介导的正反馈回路对暴露于减毒和低毒力ASFV毒株的细胞中干扰素信号通路激活的作用。此外，我们分别揭示了以 和 的表达为特征的PAM群体，它们会产生高水平的干扰素刺激基因（ISG）和IL18，以调节宿主对不同毒力ASFV毒株的反应。总体而言，我们的数据为不同ASFV毒株感染时复杂的宿主 - 病毒相互作用提供了见解，这可能为有效抗病毒策略的开发提供线索。
目前尚无关于在单细胞水平下宿主细胞暴露于不同毒力ASFV毒株时的时间转录谱的研究。在此，我们首次描绘了暴露于高毒力、减毒力和低毒力ASFV毒株的PAM中的时间病毒和宿主转录组。我们的分析表明，减毒和低毒力的ASFV毒株往往比高毒力毒株表现出更高的病毒载量，这可能是由于RNA聚合酶亚基基因表达上调所致。我们还发现了通过IRF7介导的干扰素信号通路的正反馈回路，并分别鉴定了以 和 为特征的PAM群体，它们会产生高水平的ISG和 来调节宿主对不同毒力ASFV毒株的反应。我们的研究描绘了不同毒力ASFV毒株间宿主 - 病毒动态的全面单细胞图谱，并将为未来研究提供重要资源。
