Transcriptome profiling in swine macrophages infected with African swine fever virus at single-cell resolution

文献类型： 外文期刊

第一作者： Zheng, Yuxuan

作者： Zheng, Yuxuan;Li, Shi-Hua;Wang, Qihui;Bi, Yuhai;Gao, George F.;Li, Su;Yu, Shaoxiong;Zhang, Kehui;Qu, Liang;Sun, Yuan;Qiu, Hua-Ji;Li, Su;Yu, Shaoxiong;Zhang, Kehui;Qu, Liang;Sun, Yuan;Qiu, Hua-Ji;Wang, Qihui;Bi, Yuhai;Gao, George F.;Tang, Fuchou;Tang, Fuchou;Tang, Fuchou

作者机构：

关键词： African swine fever virus; single-cell RNA sequencing; macrophage; virus-host interaction; tumor necrosis factor alpha

期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：12.779； 五年影响因子：13.45 ）

ISSN： 0027-8424

年卷期： 2022 年 119 卷 19 期

页码：

收录情况： SCI

摘要： African swine fever virus (ASFV) is the causative agent of African swine fever, a highly contagious and usually fatal disease in pigs. The pathogenesis of ASFV infection has not been clearly elucidated. Here, we used single-cell RNA-sequencing technology to survey the transcriptomic landscape of ASFV-infected primary porcine alveolar macrophages. The temporal dynamic analysis of viral genes revealed increased expression of viral transmembrane genes. Molecular characteristics in the ASFV-exposed cells exhibited the activation of antiviral signaling pathways with increased expression levels of interferon-stimulated genes and inflammatory- and cytokine-related genes. By comparing infected cells with unexposed cells, we showed that the unfolded protein response (UPR) pathway was activated in low viral load cells, while the expression level of UPR-related genes in high viral load cells was less than that in unexposed cells. Cells infected with various viral loads showed signature transcriptomic changes at the median progression of infection. Within the infected cells, differential expression analysis and coregulated virus-host analysis both demonstrated that ASFV promoted metabolic pathways but inhibited interferon and UPR signaling, implying the regulation pathway of viral replication in host cells. Furthermore, our results revealed that the cell apoptosis pathway was activated upon ASFV infection. Mechanistically, the production of tumor necrosis factor alpha (TNF-alpha) induced by ASFV infection is necessary for cell apoptosis, highlighting the importance of TNF-alpha in ASFV pathogenesis. Collectively, the data provide insights into the comprehensive host responses and complex virus-host interactions during ASFV infection, which may instruct future research on antiviral strategies.

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