期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2201288119
关键词
African swine fever virus; single-cell RNA sequencing; macrophage; virus-host interaction; tumor necrosis factor alpha
资金
- National Key R&D Program of China [2021YFD1800100]
- Intramural Special Grants for African Swine Fever Research from the Chinese Academy of Sciences (CAS) [KJZD-SW-L06-01]
- National Natural Science Foundation of China (NSFC) [31941010, 32072866]
- Strategic Priority Research Program of the CAS [XDB29010202, XDB29010102]
- NSFC Outstanding Young Scholars [31822055]
- Youth Innovation Promotion Association of the CAS [Y2021034, 2017122]
- Natural Science Foundation of Heilongjiang Province of China [JQ2020C002]
African swine fever virus (ASFV) infection leads to increased expression of viral transmembrane genes, activation of antiviral signaling pathways and inflammatory response. Cells infected with different viral loads show distinct transcriptomic changes during infection. Furthermore, ASFV infection activates the cell apoptosis pathway.
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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