Z-conformation nucleic acid binding protein 1 (ZBP1), a powerful innate immune sensor, has been identified as the important signaling initiation factor in innate immune response and the multiple inflammatory cell death known as PANoptosis. The initiation of ZBP1 signaling requires recognition of left-handed double-helix Z-nucleic acid (includes Z-DNA and Z-RNA) and subsequent signaling transduction depends on the interaction between ZBP1 and its adapter proteins, such as TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1), and RIPK3. ZBP1 activated innate immunity, including type-I interferon (IFN-I) response and NF-κB signaling, constitutes an important line of defense against pathogenic infection. In addition, ZBP1-mediated PANoptosis is a double-edged sword in anti-infection, auto-inflammatory diseases, and tumor immunity. ZBP1-mediated PANoptosis is beneficial for eliminating infected cells and tumor cells, but abnormal or excessive PANoptosis can lead to a strong inflammatory response that is harmful to the host. Thus, pathogens and host have each developed multiplex tactics targeting ZBP1 signaling to maintain strong virulence or immune homeostasis. In this paper, we reviewed the mechanisms of ZBP1 signaling, the effects of ZBP1 signaling on host immunity and pathogen infection, and various antagonistic strategies of host and pathogen against ZBP1. We also discuss existent gaps regarding ZBP1 signaling and forecast potential directions for future research.

Background: African swine fever virus (ASFV) is a highly lethal virus that can infect porcine alveolar macrophages (PAMs). Since ASFV, China has dealt with a heavy blow to the pig industry. However, the effect of infection of ASFV strains isolated from China on PAM transcription level is not yet clarified. Methods: In this study, RNA sequencing (RNA-seq) was used to detect the differential expression of genes in PAMs at different time points after ASFV-CN/GS/2018 infection. The fluorescent quantitative polymerase chain reaction (qPCR) method was used to confirm the altered expression of related genes in PAMs infected with ASFV. Results: A total of 1154 differentially expressed genes were identified after ASFV-CN/GS/2018 infection, of which 816 were upregulated, and 338 were downregulated. GO and KEGG analysis showed that these genes were dynamically enriched in various biological processes, including innate immune response, inflammatory response, chemokines, and apoptosis. Furthermore, qPCR verified that the DEAD box polypeptide 58 (DDX58), Interferon-induced helicase C domain-containing protein 1 (IFIH1), Toll-like receptor 3 (TLR3), and TLR7 of PAMs were upregulated after ASFV infection, while TLR4 and TLR6 had a significant downward trend during ASFV infection. The expression of some factors related to antiviral and inflammation was altered significantly after ASFV infection, among which interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), IFIT2, Interleukin-6 (IL-6) were upregulated, and Ewing’s tumor-associated antigen 1 homolog (ETAA1) and Prosaposin receptor GPR37 (GPR37) were downregulated. In addition, we discovered that ASFV infection is involved in the regulation of chemokine expression in PAMs, and the chemokines, such as C-X-C motif chemokine 8 (CXCL8) and CXCL10, were upregulated after infection. However, the expression of chemokine receptor C-X-C chemokine receptor type 2 (CXCR2) is downregulated. Also, that the transcriptional levels of pro-apoptotic and anti-apoptotic factors changed after infection. Conclusions: After ASFV-CN/GS/2018 infection, the expression of some antiviral and inflammatory factors in PAMs changed significantly. The ASFV infection may activates the RLR and TLR signaling pathways. In addition, ASFV infection is involved in regulating of chemokine expression in PAMs and host cell apoptosis.

DEAD-box decapping enzyme 20 (DDX20) is a putative RNA-decapping enzyme that can be identified by the conserved motif Asp–Glu–Ala–Asp (DEAD). Cellular processes involve numerous RNA secondary structure alterations, including translation initiation, nuclear and mitochondrial splicing, and assembly of ribosomes and spliceosomes. DDX20 reportedly plays an important role in cellular transcription and post-transcriptional modifications. On the one hand, DDX20 can interact with various transcription factors and repress the transcriptional process. On the other hand, DDX20 forms the survival motor neuron complex and participates in the assembly of snRNP, ultimately affecting the RNA splicing process. Finally, DDX20 can potentially rely on its RNA-unwinding enzyme function to participate in microRNA (miRNA) maturation and act as a component of the RNA-induced silencing complex. In addition, although DDX20 is not a key component in the innate immune system signaling pathway, it can affect the nuclear factor kappa B (NF-κB) and p53 signaling pathways. In particular, DDX20 plays different roles in tumorigenesis development through the NF-κB signaling pathway. This process is regulated by various factors such as miRNA. DDX20 can influence processes such as viral replication in cells by interacting with two proteins in Epstein–Barr virus and can regulate the replication process of several viruses through the innate immune system, indicating that DDX20 plays an important role in the innate immune system. Herein, we review the effects of DDX20 on the innate immune system and its role in transcriptional and post-transcriptional modification processes, based on which we provide an outlook on the future of DDX20 research in innate immunity and viral infections.

African swine fever virus (ASFV) is prevalent in many countries and is a contagious and lethal virus that infects pigs, posing a threat to the global pig industry and public health. The interaction between the virus and the host is key to unlocking the mystery behind viral pathogenesis. A comprehensive understanding of the viral and host protein interaction may provide clues for developing new antiviral strategies. Here, we show a network of ASFV MGF360-9L protein interactions in porcine kidney (PK-15) cells. Overall, 268 proteins that interact with MGF360-9L are identified using immunoprecipitation and liquid chromatography–mass spectrometry (LC-MS). Accordingly, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, and the protein–protein interaction (PPI) network was created. It was speculated that the cellular proteins interacting with MGF360-9L are involved in protein binding, metabolism, and the innate immune response. Proteasome subunit alpha type (PSMA3), 26S protease regulatory subunit 4 (PSMC1), autophagy and beclin 1 regulator 1 (AMBRA1), and DEAD-box helicase 20 (DDX20) could interact with MGF360-9L in vitro. PSMA3 and PSMC1 overexpression significantly promoted ASFV replication, and MGF360-9L maintained the transcriptional level of PSMA3 and PSMC1. Here, we show the interaction between ASFV MGF360-9L and cellular proteins and elucidate the virus–host interaction network, which effectively provides useful protein-related information that can enable further study of the potential mechanism and pathogenesis of ASFV infection.

• Using the isobaric tags for relative and absolute quantitation combined with liquid chromatography-mass spectrometry, 286 upregulated differentially expressed proteins and 69 downregulated differentially expressed proteins were identified in BMDM infected with ASFV. • Overexpression of PIK3AP1 inhibits ASFV replication in a way independent of the PI3K-Akt pathway. • ASFV MGF360-9L interacts with PIK3AP1 and decreases its protein expression level. • The PI3K-Akt pathway was identified as a posotive regulator on genotype Ⅱ ASFV replication in natural host cells.