When ASFV Infection Meets the cGAS-STING Signaling Pathway

Chen, Songbiao; Shang, Ke; Wei, Ying; Chen, Jian; Yu, Zuhua; He, Lei; Ding, Ke

doi:https://doi.org/10.1155/2024/6898157

Transboundary and Emerging Diseases

On this page

Abstract Introduction Conclusions Conflicts of Interest Authors’ Contributions Acknowledgments References Copyright Related Articles

Review Article | Open Access

Volume 2024 | Article ID 6898157 | https://doi.org/10.1155/2024/6898157

When ASFV Infection Meets the cGAS-STING Signaling Pathway

Songbiao Chen,^1,2,3,4Ke Shang,^1,2,3Ying Wei,^1,2,3Jian Chen,^1,2,3Zuhua Yu,^1,2,3Lei He ,^1,2,3and Ke Ding^1,2,3,4

Academic Editor: Chunfu Zheng

Received18 Jan 2024

Revised18 Mar 2024

Accepted23 Mar 2024

Published08 Apr 2024

Abstract

The African swine fever virus (ASFV) has the ability to infect both wild boars and domestic pigs, regardless of their breeds or ages, often resulting in a mortality rate of 100%. Host innate immunity is the most important defense weapon against invasion of pathogenic microbial infection. cGAS-STING signaling pathway is one of the greatest discoveries of the twenty-first century, which is crucial in host’s innate immune response. Recent studies have found that the interaction between cGAS/STING pathway and ASFV plays a key role during ASFV infection. At the same time, ASFV has also evolved different strategies to evade the killing of the host cGAS/STING pathway and promote its survival. Here, we review the latest progress in the interaction between ASFV infection, cGAS/STING pathways, and their related molecular mechanisms, aiming to provide new ideas for further research on the pathogenesis of ASFV, the development of vaccines and therapeutic drugs.

1. Introduction

African swine fever virus (ASFV) causes a devastating disease in pigs [1, 2], it was the first outbreak in Kenya and was reported in 1921 [3]. Subsequently, ASFV was found in China on August 3, 2018 [4, 5], and soon spread across the country with unprecedented speed, which caused at least 300 million pigs estimated to have died from infection or preventive culling, with economic losses of about $100 billion [6].

ASFV infection is the product of the interaction between virus and host antiviral [7–9]. Innate immunity, also known as natural immunity or nonspecific immunity, is the most important host defense weapon against pathogenic microbial invasion [10, 11]. The immune system depends on a group of receptors known as pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and trigger the production of immune molecules and cytokines in host cells to fight pathogen microbial invasion [12]. DNA is one of the important PAMPs, once the pathogen enters the host cell, it will release its DNA into the cytoplasm. The DNA sensor cGAS is able to detect cytoplasmic DNA and promptly activate the innate immune response through the STING protein, which is mediated by interferon-stimulating factor [13, 14]. Following that, it was discovered that STING plays a role in transmitting signals for type I interferon (IFN-I) through interferon regulatory factor 3 (IRF3) [15, 16], and it was also found that STING dimerization is crucial for initiating subsequent signals [17, 18].

cGAS-STING is crucial for anti-DNA virus and RNA virus infection [19–22]. Recent studies have confirmed that cGAS-STING is essential for ASFV infection and pathogenesis. Meanwhile, ASFV has also developed a series of strategies to manipulate the host’s defense function against viral infection [23–25]. Hence, thorough investigation into ASF immune evasion theory is crucial, alongside enhancing biosafety measures to combat the ASF outbreak and expediting the creation of reliable vaccines. At present, the understanding of the pathogenesis of ASFV is incomplete, which seriously affects the effective prevention and development the efficient vaccines. Here, we review the interaction between ASFV and cGAS-STING and their related molecular mechanisms, aiming to provide new ideas for further research on the pathogenesis of ASFV and effective vaccines.

2. Overview of ASFV

ASF has spread to more than 40 countries all over the world since its discovery in 1921 [3] (Figure 1, incomplete statistics until 2020). The first indigenous case of ASF was first reported in Liaoning, China, on August 3, 2018 [4, 5], and soon spread with unprecedented speed to all 30 provinces and autonomous regions of the country within 8 months (Figure 2, updated to April 19, 2019). Vaccination is the most effective approach to prevent and control infectious diseases [26, 27]. At present, there is still a lack of safe and effective ASF vaccines, so vaccine development remains a global challenge [28]. The most prominent feature of ASFV is its ability to camouflage to evade the host immune system and establish a complete infection, which is also the key factor hindering ASF prevention, control, and development [29].

Currently available data have shown that ASFV can replication in primary cells and cell lines [30–32]. Among them, ASFV had the best proliferation in alveolar macrophages [33–35]. During infection, ASFV initially replicates in monocytes and macrophages located in the tonsil and mandibular lymph nodes, before spreading to other tissues through the bloodstream and/or lymphatic system [35]. Among, the spleen is the organ with the highest viral load and the most serious pathological manifestations in all organs of pigs. Infection with ASFV leads to the demise of numerous monocytes in the spleen, leading to suppression of interferon response and antigen expression, ultimately facilitating the prolonged infection of ASFV [36, 37]. In the initial stage of ASFV replication, virions first interact with cell surface receptors, attach to cells, and then enter into macrophages mainly through clathrin-mediated endocytosis [38, 39] and micropinocytosis [40]. Prior research has indicated that host proteins CD1d [41], CD163 [42–45], and SIGLEC1 [42] may facilitate ASFV entry into cells; however, the role of CD1a, CD163, and SIGLEC1 as ASFV receptors requires additional confirmation. After the virion enters the cell, it travels from the early endosome to the late endosome in a pH-dependent manner along the endolysosome pathway and uncoating in this place. The virus particles expose the inner envelope, allowing it to interact, and then fuse the viral membrane with the restrictive membrane of the endosome. The bare kernel can be released into the cell solutes and transported to the perinuclear viral replication factory to begin replication [46, 47].

3. Overview of cGAS-STING Signaling Pathway

cGAS was first discovered in mammalian cells in 2013 and can synthesize cGAMP as a second messenger to directly activate STING [13–48]. Following infection of host cells by pathogenic microorganisms, cGAS as a crucial DNA sensor, quickly identifies and detects foreign viral DNA in the cytoplasm, leading to the formation of a 2 : 2 dimer and the generation of 2^′,3^′-cGAMP. Subsequently, 2^′,3^′-cGAMP binds to STING on the ER membrane, triggering activation through a change in structure. Activated STING then moves from the ER to the Golgi intermediate compartment. Upon activation, STING recruits active TBK1 using its carboxyl-terminal, forming the STING-TBK1 complex on the Golgi membrane. This complex further triggers IRF3 phosphorylation, leading to IRF3 dimerization in the nucleus (Figure 3). Simultaneously, STING has the ability to directly trigger the Iκκ kinase, leading to the phosphorylation of the inhibitor of NF-κB, ultimately resulting in the degradation of the phosphorylated IκB through the ubiquitin-proteasome pathway. NF-κB enters the nucleus and phosphorylates IRF3 to induce the secretion of interferon and inflammatory cytokines to promote host anti-infective immunity [49, 50].

3.1. The cGAS-STING Signaling Pathway and Interferon

IFNs are the initial defense mechanism of the host against viral infections, with three distinct categories: IFN-I, IFN-II, and IFN-III [51, 52]. Activation of cGAS/STING can stimulate the production of IFNs, which then trigger the transcription of numerous downstream interferon-stimulating genes by interacting with various IFN receptors located on the cell membrane [53, 54]. IFN-I functions by attaching to IFN-α receptor IFNAR1 and IFNAR2, while IFN-III binds to IL-10R2 and IFNLR1. IFN-II forms a dimer through a heterodimer consisting of IFN-γ receptors IFNGR1 and IFNGR2 [55] (Figure 3). When IFN-I and IFN-III bind to receptors, it triggers the activation of janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2), resulting in the phosphorylation of signal transduction and transcriptional activators 1 and 2 (STAT1 and 2). STAT1/STAT2 combine to create a heterodimer, which then brings in IFN regulatory factor 9 (IRF9) to produce IFN-stimulating gene factor 3 (ISGF3) [56, 57] (Figure 3). When IFN-II binds to the receptor, it causes JAK1 and JAK2 tyrosine kinases to be phosphorylated, resulting in the phosphorylation of STAT1. The phosphorylated STAT1 then forms an IFN-γ activator (GAF) dimer, which activates the expression of antiviral genes [56] (Figure 3).

3.2. The cGAS-STING Signaling Pathway and Cell Death

cGAS-STING is involved not just in the release of IFN and inflammatory cytokines, but also plays a role in various cell death mechanisms including apoptosis, necroptosis, pyroptosis, and ferroptosis [58–60].

Activation of the cGAS-STING pathway may trigger cell apoptosis [61, 62]. Stimulation with IFN-β can trigger apoptosis in cells by activating JAK-STAT, inhibiting the PI3K/AKT pathway, leading to the release of cytochrome C in the cytoplasm, and subsequently activating caspase-9 through cytochrome C [63]. Meanwhile, IFN-β can also induce apoptosis dependent on caspase-8 [64], and downregulation of IRF3 can negative regulation the proapoptotic effect of IFN-I [65–67]. The levels of cGAS, STING, and NLRP3 were significantly upregulated in intervertebral disc degeneration (IDD) patients, and epigallocatechin gallate (EGCG) treatment could inhibit cell apoptosis by target cGAS/STING/NLRP3 [68, 69] (Figure 4).

The cGAS-STING signaling pathway promotes potassium efflux activation of NLRP3 and induces pyroptosis by regulating STING transport [70], although the molecular mechanism is still unknown (Figure 4). Furthermore, cGAS-STING is capable of stimulating the production of mixed kinase domain-like protein (MLKL), a crucial element in necroptosis [71]. Additionally, proapoptotic p53 can boost the phosphorylation of receptor-interacting serine/threonine kinase 3 (RIPK3) and MLKL, leading to the release of mitochondrial DNA (mtDNA) and activation of STING, ultimately resulting in necroptosis [72] (Figure 4). Ferroptosis is identified by lipid peroxidation that relies on iron, and it is triggered by STING activation due to lipid peroxidation instead of IFN signaling when faced with mtDNA stress [73, 74] (Figure 4).

3.3. The cGAS-STING Signaling Pathway and Mitochondrial Dysfunction

Mitochondria are the energy factories of living organisms [75, 76]. Additionally, mitochondria play a key role in producing reactive oxygen species (ROS) in living organisms, particularly within the electron transport system (ETS) [77]. Under normal physiological conditions, these ROS may be secondary messengers that control the intracellular signal transduction cascade [78–80]. However, large amounts of ROS production can lead to oxidative stress [75].

ROS production and Ca²⁺ ion accumulation can trigger the activation of mitochondrial permeability transition pore (mPTP), resulting in the release of proapoptotic molecules like cytochrome C, ultimately leading to apoptosis or necroptosis (Figure 5). Apoptosis leads to the creation of large pores in the mitochondrial outer membrane (MOM) by BAX and BAK [81, 82], allowing mtDNA to move from the pore to the cytoplasm via the cGAS-STING pathway, activating the innate immune response [83].

4. Interaction between cGAS-STING Signaling Pathway and African Swine Fever Virus

Viral infection depends on the interaction between virus and host proteins. The ASFV p72 protein is a key element of the ASFV capsid, which is essential for virus attachment and entry [84–86]. Recent research indicates that p72 has the ability to bind with CD63, B2M, YTHDF2, etc., cellular proteins. The bioinformatics analysis of Go enrichment and protein interaction network revealed that the host proteins played important roles in virus attachment, invasion, replication, assembly, and immune regulation [87]. Furthermore, Sun et al. [88] also screened that p72 can interact with 2^′,5^′-oligoadenylate synthetase gene 1 (OAS1), which is a interferon-stimulating gene mediated by cGAS-STING activation. After their interaction, TRIM21 is recruited through the ubiquitin-proteasome pathway to degrade p72 at the K63 site, further destroying the assembly of mature ASFV particles and reducing the production of mature virions [88]. Wu et al. [89] found that the protein–protein interaction (PPI) network between ASFV and host immune pathways revealed that certain genes such as A151R, MGF360-11 L, E165R, G1340L, MGF505-3R, and A137R have a notable suppressive impact on IFN-β production. Additionally, K421R, MGF360-11L, EP364R, C147L, A151R, and A137R were shown to significantly inhibit NF-κB production [89]. IFN-β and NF-κB are identified as downstream components of the cGAS-STING pathway, indicating that ASFV might manipulate the host cGAS-STING pathway by targeting these proteins to suppress the host immune response and enhance viral replication.

ASFV can target cGAS-STING [90], NF-κB [91], TGF-β [92], ubiquitination [93], and apoptosis [94] signaling pathway promotes viral replication. The cGAS-STING pathway is crucial in defending against DNA viruses in the host and is the most extensively researched ASFV pathway in terms of host pathogenicity and immune evasion. cGAS-STING has strict and fine regulations in space and time to ensure that while eliminating pathogen infection, it avoids damage to the body due to insufficient or excessive immune response [95].

Replication strategies of ASFV strains and cell tropism vary widely [25]. Over the long course of evolution, ASFV encodes and expresses multiple immune escape proteins to antagonize the host immune response. The escape of ASFV to the natural immune system of the host is an important strategy for causing persistent infection of the virus, and it is also an important reason for the low immune protection and persistent infection during the development of live attenuated vaccine [96]. Earlier research has shown that the ASFV genetic material is capable of producing various viral proteins that disrupt the production of host cell proteins and disrupt pathways, ultimately hindering and avoiding the host’s immune response while promoting its own growth and spread [97, 98] (Table 1).

Below, we will explain how ASFV hinders IFN-I and enhances viral replication by interacting with signal molecules on various cGAS-STING signaling pathways at the molecular level.

4.1. Targeting cGAS Inhibits the Molecular Mechanism of cGAS-STING Activation

cGAS, also known as C6ORF150 or MB21D1, is a member of the cGAS/DNCV-like nucleotide transferase (CD-NTase) superfamily. The cGAS gene is well-preserved across human, mouse, pig, and chicken species (Figure 6). The catalytic domain is a two-leaf structure composed of overlapping nucleotide transferase core domain (NTase) and Mab21 domain. Including a central catalytic domain and two different positively charged surfaces [125, 126]. It functions as a DNA receptor in mammals, can recognize cytoplasmic DNA and produce cGAMP, and activate STING regulate the secretion of downstream IFN-I and other cytokines.

QP383R of ASFV is an unnamed protein composed of 383 amino acids. QP383R inhibits the inflammatory response during ASFV infection by inhibiting AIM2 inflammasome activation [127] (Figure 7). Additionally, QP383R functions as a suppressor of cGAS/STING-driven innate immune responses, with elevated levels of QP383R leading to reduced activation of cGAS-STING by dsDNA [99] (Figure 7). Further studies showed that QP383R promoted the palmitoylation of cGAS through its C-terminal (284-383 aa) interaction with the nucleotide transferase (NTase) domain of cGAS, inhibited the binding of cGAS to ligand DNA and cGAS dimerization reduced the downstream interferon reaction [99] (Figure 7).

4.2. Targeting 2^′,3^′-cGAMP Inhibits the Molecular Mechanism of cGAS-STING Activation

Wu et al. [14] discovered cGAMP as a natural signaling molecule for innate immunity in response to cytoplasmic DNA in 2012 and confirmed its presence in mammalian cells. Subsequently, it was confirmed that cGAMP is the catalytic product of cGAS (the substrate is ATP and GTP) by liquid chromatography–mass spectrometry, and the small molecule cGAMP directly binds and activates STING to induce IFN-I production [13].

After ASFV infection, cGAS recognizes viral DNA and synthesizes 2^′,3^′-cGAMP, triggering the production of interferon to interfere with viral replication. ASFV protein EP364R and C129R have the ability to hinder the host antiviral response triggered by 2^′,3^′-cGAMP. These proteins not only suppress IFN-I secretion by interacting with 2^′,3^′-cGAMP but also increase their effectiveness in degrading 2^′,3^′-cGAMP [101] (Figure 7). At the same time, ASFV EP364R has a homologous domain with the interaction 2^′,3^′-cGAMP with STING and is able to competitively with 2^′,3^′-cGAMP [101] (Figure 7). ASFV B175L can interfere with the interaction between cGAMP and STING by interacting with cGAMP, thereby inhibiting downstream signaling of IFN-mediated antiviral response [102].

4.3. Targeting STING Inhibits the Molecular Mechanism of cGAS-STING Activation

STING is a 40 kDa adaptor protein located in the endoplasmic reticulum or Golgi apparatus [128, 129]. STING consists of a transmembrane N-terminal domain and a globular C-terminal domain (CTD), and the N-terminal contains four transmembrane helical structures (TM1−4) anchored to the endoplasmic reticulum or other organelles. The C-terminal CTD region is comprised of a ligand-binding section (LBD) and a C-terminal tail segment (CTT). LBD combines 2^′,3^′-cGAMP and CDNs. CTT can bind TBK1 [130, 131].

ASFV MGF505-11R suppresses the activation of IFN-β and ISRE by cGAS, IRF7, IRF3, STING, IKK-ε, TBK1, leading to decreased mRNA transcription of IFN-β, ISG15, and ISG56 [106] (Figure 8). MGF505-11R was discovered to have the ability to degrade STING, with the functional domains responsible for this function being 1-191 aa and 182-360 aa of MGF505-11R [106] (Figure 8). E248R binding to STING and blocking the expression of STING suppresses to promote viral replication [105] (Figure 8). ASFV p17 (39-59aa) inhibited the cGAS-STING pathway by interfering with STING recruitment of TBK1 and IKKɛ through its interaction with STING [107] (Figure 8). ASFV L83L overexpression suppresses IFN-β promoter and ISRE function, while reducing L83L levels increases ISGs expression and IRF3 phosphorylation in primary porcine alveolar macrophages [103]. L83L enhances the autophagolysosomal breakdown of STING by engaging cGAS and STING to bring in Tollip, inhibiting the phosphorylation of TBK1, IRF3, and IKB-α, which are downstream signaling molecules [103] (Figure 8). The ASFV E184L protein suppresses the innate immune responses of the host by interacting with the STING-mediated signaling pathway. E184L hinders the dimerization and oligomerization of STING by interacting with it [108]. Moreover, E184L hinders the assembly of the STING-TBK1-IRF3 complex, leading to the suppression of STING phosphorylation, IRF3 dimerization, and movement into the nucleus [108] (Figure 8). ASFV B175L can interfere with the interaction between cGAMP and STING by specifically interacting with R238 and Y240 amino acids of STING, thereby inhibiting downstream signal transduction of IFN-mediated antiviral response [102]. pH240R binds to the N-terminal transmembrane region of STING, preventing its oligomerization and movement from the endoplasmic reticulum to the Golgi apparatus. This interaction also blocks the phosphorylation of IRF3 and TBK1, leading to reduced production of type I interferon and ultimately promoting viral replication [132].

4.4. Targeting TBK1 Inhibits the Molecular Mechanism of cGAS-STING Activation

TBK1 is the center of antiviral innate immune signal transduction. On the one hand, TBK1 can be activated by multiple PRRS. Conversely, TBK1, a crucial enzyme, phosphorylates multiple targets like IRF3 and IRF7 when activated, triggering the start of an antiviral innate immune reaction.

ASFV DP96R blocks cGAS/STING and TBK1, while not affecting IRF3-induced IFN-β and ISRE promoter activation [117]. DP96R inhibits TBK1 phosphorylation and inhibits its induced antiviral response [117]. M1249L blocks TBK1 phosphorylation induced by excessive cGAS and STING expression [110]. M1249L can also colocate and interact with IRF3 to induce IRF3 degradation and inhibit host antiviral response through the lysosome pathway [110] (Figure 8). ASFV pI215L is a viral E2 ubiquitination binding enzyme. Reducing pI215L levels suppresses ASFV replication and boosts the production of IFN-β [111]. Additionally, pI215L induces polyubiquitination at K63 of TBK1, leading to the inhibition of type I IFN production through its interaction with RING finger protein 138 (RNF138) [111] (Figure 8). MGF360-11L binds with TBK1 and IRF7, leading to the degradation of both TBK1 and IRF7 [118]. Meanwhile, MGF360-11L also inhibits TBK1 and IRF3 phosphorylation to antagonize the molecular mechanism of type I interferon-mediated antiviral activity [118]. MGF505-7R inhibits antiviral activity by interacting with IRF7 and TBK1, degrading IRF7 via autophagy, cysteine, and proteasome pathways, and degrading TBK1 via the proteasome pathway [133] (Figure 8). Deletion of MGF110-9L reduced the virulence of ASFV in pigs and provided complete protection against the attack of parental lethal ASFV [119]. It was found that MGF110-9L/505-7R blocks the degradation of TBK1 through the autophagy pathway and promotes viral replication by targeting the autophagy associated protein PIK3C2B. MGF110-9L promoted the degradation of TBK1 through the autophagy pathway [119] Figure 8). PA151R negatively regulates IFN-I production. Additional research revealed that PA151R and TBK1 engage in a competitive interaction with the E3 enzyme TNF receptor-related protein TRAF6, leading to the suppression of TRAF6 expression via the apoptosis pathway. This ultimately results in the inhibition of TBK1 phosphorylation and the suppression of ASFV replication [113]. PA151R negatively regulates IFN-I production. Additional research revealed that PA151R and TBK1 engage in a competitive interaction with the E3 enzyme TNF receptor-related protein TRAF6, leading to the suppression of TRAF6 expression via the apoptosis pathway. This ultimately results in the inhibition of TBK1 phosphorylation and the suppression of ASFV replication [109].

4.5. Targeting IRF3 Inhibits the Molecular Mechanism of cGAS-STING Activation

IRF3 is expressed constitutively in various tissues and cells. When the cells are resting, IRF3 is in the cytoplasm and a self-inhibition state. Following the intrusion of the virus, TBK1 and IKKε phosphorylate numerous serine and threonine sites at the C-terminus of IRF3. After phosphorylation, conformational changes occur in IRF3, and the C-terminal combines to form a dimer, which migrates from the cytoplasm to the nucleus. CBP, a coactivator that binds, stimulates the production of IFN-I.

Another study showed that the molecular mechanism of ASFV DP96R inhibits IRF3-mediated antiviral immune response. DP96R blocks the interaction between activated IRF3 and KPNA, inhibiting the translocation of IRF3 to the nucleus by binding to a crucial site on KPNA within IRF3 [120]. DP96R overexpression enhances DNA and RNA virus replication by inhibiting the cGAS-STING signaling pathway and suppressing antiviral gene transcription. Knocking out DP96R with DP96R-specific siRNA leads to increased IFN and ISG transcription during ASFV infection [120]. ASFV pS273R is a cysteine protease specific to SUMO-1, and it hinders the production of IFN-I by interacting with IRF3 [112], pS273R disrupts the interaction between TBK1 and IRF3, inhibiting the phosphorylation and dimerization of IRF3 [112] (Figure 8). A137-deficient ASFV virus can induce higher IFN-I production [116], and A137R interacts with TBK1 to promote autophagy-mediated TBK1 lysosomal degradation, thereby blocking IRF3 nuclear translocation, resulting in reduced IFN-I production [116] (Figure 8). The ASFV E120R protein is capable of inhibiting the phosphorylation of IRF3 and the production of IFN-I by binding to IRF3 and preventing its recruitment to TBK1 [121] (Figure 8). Elimination of the MGF505-7R gene from ASFV may lead to increased production of IL-1β and IFN-β. MGF505-7R hinders NF-κB activation by interacting with IKKα and suppresses inflammasome formation by binding to NLRP3, leading to decreased IL-1β production [134]. MGF505-7R can interact with IRF3, preventing the nuclear translocation of IRF3, and increasing the expression of autophagy-related protein ULK1 to break down STING [104–134] (Figure 8). pD129L inhibits the IFN signaling pathway by disrupting the interaction between transcriptional coactivators p300 and IRF3, leading to the suppression of IFN-I production and enhancement viral replication [124].

5. Conclusions and Perspectives

The development of a novel and highly effective ASFV vaccine is the primary problem for researchers around the world. At present, the research progress of live attenuated ASFV vaccine, adenovirus vaccine, recombinant pseudorabies virus vaccine, and antiviral drugs has been made, and the vaccines and drugs have certain protective effects against the attack and replication of ASFV parent strains [90, 135–141]. For example, the attenuated ASFV vaccine HLJ/18-7GD was capable of providing effective immune protection against different wild strains [142]; ASFV genotype II GeorgiaΔDP148RΔK145RΔEP153R-CD2v mutant Q96R/K108D attenuated strain is able to provide 83%–100% immune protective efficiency against parental strain for different doses of challenge [143]. These results showed that HLJ/18-7GD and GeorgiaΔDP148RΔK145RΔEP153R-CD2v_mutantQ96R/K108D have potential as candidate vaccines. It is worth noting that, vaccines are needed to provide cross-protection against different ASFV genotypes.

The most striking feature of host defense is that once infected with these viruses, cells can rapidly activate cGAS-STING to produce an innate immune response to ASFV to prevent viral infection. The host defense mechanism is essential for the balance between survival and death of the host. However, the lack of detailed mechanisms of ASFV and host interaction has greatly limited the development of effective vaccines. ASFV proteins inhibit IFN-β production by targeting different molecules of the cGAS-STING pathway. Therefore, it maybe impractical to develop drugs that target different viral virulence proteins and apply them to clinical prevention and control. Kuchitsu et al. [144] found that the host VPS protein can promote the transport of STING from the Golgi apparatus to the lysosome, reduce the residence time of STING in the Golgi apparatus, and thus inhibit the immune activation state of the host. In the future, the differences in susceptibility and pathogenicity of ASFV in different animals can also be studied clinically, and the key host proteins that differ in susceptibility and pathogenicity of ASFV can be screened using high-throughput and single-cell sequencing methods, to establish a knowledge base on the host susceptibility system of ASFV.

mRNA vaccines (the third-generation vaccine) have made a great contribution in blocking SARS-CoV-2 infection and transmission [145–147]. mRNA vaccines activate the dual mechanism of humoral and T cell immunity, strong immunogenicity, no need for adjuvants, and ease of mass production support the key advantages of global supply [148, 149]. There are also many studies on mRNA vaccines for DNA viruses, such as the monkeypox virus [150–155] and Epstein–Barr virus [156, 157], which suggests that mRNA vaccines of DNA viruses have a good prospect. ASFV p34, p72, p54, p30, and CD2v are the main immunogenic proteins and can effectively stimulate the body’s immune response [143, 158, 159]. Meanwhile, Deletion B125R [160], C84L [161], L11L/L7L [162], DP71L [163], DP96R [163], B119L [164], and DP148R [163] significantly reduced the virulence of the virus and showed partial or complete protection against infection with ASFV strains. Besides, a lot of conserved B cell linear epitope in pB602L [165], p34 [166], p30 [167], pA104R [168], and p72 [169] have been identified. About the ASFV vaccine: (1) we can screen the optimal deletion combination of virulence genes (B125R, C84L, L11L/L7L, DP71L, DP96R, B119L, and DP148R) to obtain attenuated and attenuated vaccines; (2) we can concatenate mRNA vaccines that express different immunogenic proteins (p34, p72, p54, p30, and CD2v); and (3) we can also tandem mRNA vaccines that express different B cell linear epitopes (pB602L, p34, p30, pA104R, and p72) of the same immunogenic protein.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Songbiao Chen contributed to conception and project administration. Ke Shang, Lei He, and Ke Ding contributed to design and funding support. Songbiao Chen and Ke Shang wrote the original manuscript and revised the article. Jian Chen and Lei He contributed to language polishing. Ying Wei, Zuhua Yu, and Jian Chen prepared the figures and tables.

Acknowledgments

This work was supported by the Henan Province Science and Technology Research and Development Plan Joint Foundation (232103810029) and the Natural Science Foundation of Henan (232300421263).

References

L. K. Dixon, H. Sun, and H. Roberts, “African swine fever,” Antiviral Research, vol. 165, pp. 34–41, 2019.
View at: Publisher Site | Google Scholar
X. Duan, Y. Ru, W. Yang et al., “Research progress on the proteins involved in African swine fever virus infection and replication,” Frontiers in Immunology, vol. 13, Article ID 947180, 2022.
View at: Publisher Site | Google Scholar
R. E. Montgomery, “On a form of swine fever occurring in British East Africa (Kenya Colony),” Journal of Comparative Pathology and Therapeutics, vol. 34, pp. 159–191, 1921.
View at: Publisher Site | Google Scholar
S. Ge, J. Li, X. Fan et al., “Molecular characterization of African swine fever virus, China, 2018,” Emerging Infectious Diseases, vol. 24, no. 11, pp. 2131–2133, 2018.
View at: Publisher Site | Google Scholar
X. Zhou, N. Li, Y. Luo et al., “Emergence of African swine fever in China, 2018,” Transboundary and Emerging Diseases, vol. 65, no. 6, pp. 1482–1484, 2018.
View at: Publisher Site | Google Scholar
A. Ayanwale, S. Trapp, R. Guabiraba, I. Caballero, and F. Roesch, “New insights in the interplay between African swine fever virus and innate immunity and its impact on viral pathogenicity,” Frontiers in Microbiology, vol. 13, Article ID 958307, 2022.
View at: Publisher Site | Google Scholar
H. Sun, Q. Niu, J. Yang et al., “Transcriptome profiling reveals features of immune response and metabolism of acutely infected, dead and asymptomatic infection of African swine fever virus in pigs,” Frontiers in Immunology, vol. 12, Article ID 808545, 2021.
View at: Publisher Site | Google Scholar
Q. Xue, H. Liu, Z. Zhu et al., “African swine fever virus regulates host energy and amino acid metabolism to promote viral replication,” Journal of Virology, vol. 96, no. 4, Article ID e0191921, 2022.
View at: Publisher Site | Google Scholar
X. Yang, X. Bie, H. Liu et al., “Metabolomic analysis of pig spleen reveals African swine fever virus infection increased acylcarnitine levels to facilitate viral replication,” Journal of Virology, vol. 97, no. 8, Article ID e0058623, 2023.
View at: Publisher Site | Google Scholar
P. J. Kranzusch, “Editorial overview: evolution of antiviral defense,” Current Opinion in Microbiology, vol. 75, Article ID 102352, 2023.
View at: Publisher Site | Google Scholar
W. Ma, C. L. Loving, and J. P. Driver, “From snoot to tail: a brief review of influenza virus infection and immunity in pigs,” The Journal of Immunology, vol. 211, no. 8, pp. 1187–1194, 2023.
View at: Publisher Site | Google Scholar
M. Carty, C. Guy, and A. G. Bowie, “Detection of viral infections by innate immunity,” Biochemical Pharmacology, vol. 183, Article ID 114316, 2021.
View at: Publisher Site | Google Scholar
L. Sun, J. Wu, F. Du, X. Chen, and Z. J. Chen, “Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway,” Science, vol. 339, no. 6121, pp. 786–791, 2013.
View at: Publisher Site | Google Scholar
J. Wu, L. Sun, X. Chen et al., “Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA,” Science, vol. 339, no. 6121, pp. 826–830, 2013.
View at: Publisher Site | Google Scholar
H. Ishikawa and G. N. Barber, “STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling,” Nature, vol. 455, no. 7213, pp. 674–678, 2008.
View at: Publisher Site | Google Scholar
B. Zhong, Y. Yang, S. Li et al., “The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation,” Immunity, vol. 29, no. 4, pp. 538–550, 2008.
View at: Publisher Site | Google Scholar
W. Sun, Y. Li, L. Chen et al., “ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization,” Proceedings of the National Academy of Sciences, vol. 106, no. 21, pp. 8653–8658, 2009.
View at: Publisher Site | Google Scholar
R. Zhang, W. Yang, H. Zhu, J. Zhai, M. Xue, and C. Zheng, “NLRC4 promotes the cGAS-STING signaling pathway by facilitating CBL-mediated K63-linked polyubiquitination of TBK1,” Journal of Medical Virology, vol. 95, no. 8, Article ID e29013, 2023.
View at: Publisher Site | Google Scholar
Y. M. Fan, Y. L. Zhang, H. Luo, and Y. Mohamud, “Crosstalk between RNA viruses and DNA sensors: role of the cGAS-STING signalling pathway,” Reviews in Medical Virology, vol. 32, no. 5, Article ID e2343, 2022.
View at: Publisher Site | Google Scholar
M. Oliveira, D. R. Rodrigues, V. Guillory et al., “Chicken cGAS senses fowlpox virus infection and regulates macrophage effector functions,” Frontiers in Immunology, vol. 11, Article ID 613079, 2021.
View at: Publisher Site | Google Scholar
W. Zheng, Z. Zhou, Y. Rui et al., “TRAF3 activates STING-mediated suppression of EV-A71 and target of viral evasion,” Signal Transduction and Targeted Therapy, vol. 8, no. 1, Article ID 79, 2023.
View at: Publisher Site | Google Scholar
Q. Zhu, H. Hu, H. Liu, H. Shen, Z. Yan, and L. Gao, “A synthetic STING agonist inhibits the replication of human parainfluenza virus 3 and rhinovirus 16 through distinct mechanisms,” Antiviral Research, vol. 183, Article ID 104933, 2020.
View at: Publisher Site | Google Scholar
W.-R. He, J. Yuan, Y.-H. Ma et al., “Modulation of host antiviral innate immunity by African swine fever virus: a review,” Animals, vol. 12, no. 21, Article ID 2935, 2022.
View at: Publisher Site | Google Scholar
J. Wang, X.-J. Shi, H.-W. Sun, and H.-J. Chen, “Insights into African swine fever virus immunoevasion strategies,” Journal of Integrative Agriculture, vol. 19, no. 1, pp. 11–22, 2020.
View at: Publisher Site | Google Scholar
S. Niu, Y. Guo, X. Wang et al., “Innate immune escape and adaptive immune evasion of African swine fever virus: a review,” Virology, vol. 587, Article ID 109878, 2023.
View at: Publisher Site | Google Scholar
M. J. Levin, A. Ustianowski, S. De Wit et al., “Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for prevention of Covid-19,” New England Journal of Medicine, vol. 386, no. 23, pp. 2188–2200, 2022.
View at: Publisher Site | Google Scholar
A. T. Moin, R. B. Patil, T. Tabassum et al., “Immunoinformatics approach to design novel subunit vaccine against the epstein-barr virus,” Microbiology Spectrum, vol. 10, no. 5, Article ID e0115122, 2022.
View at: Publisher Site | Google Scholar
P. J. Sánchez-Cordón, M. Montoya, A. L. Reis, and L. K. Dixon, “African swine fever: a re-emerging viral disease threatening the global pig industry,” The Veterinary Journal, vol. 233, pp. 41–48, 2018.
View at: Publisher Site | Google Scholar
X. Zheng, S. Nie, and W.-H. Feng, “Regulation of antiviral immune response by African swine fever virus (ASFV),” Virologica Sinica, vol. 37, no. 2, pp. 157–167, 2022.
View at: Publisher Site | Google Scholar
I. Nurmoja, A. Petrov, C. Breidenstein et al., “Biological characterization of African swine fever virus genotype II strains from north-eastern Estonia in European wild boar,” Transboundary and Emerging Diseases, vol. 64, no. 6, pp. 2034–2041, 2017.
View at: Publisher Site | Google Scholar
I. Vallee, S. W. G. Tait, and P. P. Powell, “African swine fever virus infection of porcine aortic endothelial cells leads to inhibition of inflammatory responses, activation of the thrombotic state, and apoptosis,” Journal of Virology, vol. 75, no. 21, pp. 10372–10382, 2001.
View at: Publisher Site | Google Scholar
L. Zsak, Z. Lu, T. G. Burrage et al., “African swine fever virus multigene family 360 and 530 genes are novel macrophage host range determinants,” Journal of Virology, vol. 75, no. 7, pp. 3066–3076, 2001.
View at: Publisher Site | Google Scholar
G. Franzoni, S. Dei Giudici, and A. Oggiano, “Infection, modulation and responses of antigen-presenting cells to African swine fever viruses,” Virus Research, vol. 258, pp. 73–80, 2018.
View at: Publisher Site | Google Scholar
G. Franzoni, S. P. Graham, S. D. Giudici et al., “Characterization of the interaction of African swine fever virus with monocytes and derived macrophage subsets,” Veterinary Microbiology, vol. 198, pp. 88–98, 2017.
View at: Publisher Site | Google Scholar
F. J. Salguero, “Comparative pathology and pathogenesis of African Swine fever infection in Swine,” Frontiers in Veterinary Science, vol. 7, Article ID 282, 2020.
View at: Publisher Site | Google Scholar
P. Gao, L. Zhou, J. Wu et al., “Riding apoptotic bodies for cell–cell transmission by African swine fever virus,” Proceedings of the National Academy of Sciences, vol. 120, no. 48, Article ID e2309506120, 2023.
View at: Publisher Site | Google Scholar
Z. Zhu, R. Mao, B. Liu et al., “Single-cell profiling of African swine fever virus disease in the pig spleen reveals viral and host dynamics,” Proceedings of the National Academy of Sciences, vol. 121, no. 10, Article ID e2312150121, 2024.
View at: Publisher Site | Google Scholar
B. Hernaez and C. Alonso, “Dynamin- and clathrin-dependent endocytosis in African swine fever virus entry,” Journal of Virology, vol. 84, no. 4, pp. 2100–2109, 2010.
View at: Publisher Site | Google Scholar
M. L. Valdeira and A. Geraldes, “Morphological study on the entry of African swine fever virus into cells,” Biology of The Cell, vol. 55, no. 1-2, pp. 35–40, 1985.
View at: Publisher Site | Google Scholar
E. G. Sánchez, A. Quintas, D. Pérez-Núñez et al., “African swine fever virus uses macropinocytosis to enter host cells,” PLOS Pathogens, vol. 8, no. 6, Article ID e1002754, 2012.
View at: Publisher Site | Google Scholar
X. Chen, J. Zheng, C. Liu et al., “CD1d facilitates African swine fever virus entry into the host cells via clathrin-mediated endocytosis,” Emerging Microbes & Infections, vol. 12, no. 2, Article ID 2220575, 2023.
View at: Publisher Site | Google Scholar
Q. Gao, Y. Yang, Y. Luo et al., “Adaptation of African swine fever virus to porcine kidney cells stably expressing CD163 and Siglec1,” Frontiers in Immunology, vol. 13, Article ID 1015224, 2022.
View at: Publisher Site | Google Scholar
P. Lithgow, H. Takamatsu, D. Werling, L. Dixon, and D. Chapman, “Correlation of cell surface marker expression with African swine fever virus infection,” Veterinary Microbiology, vol. 168, no. 2–4, pp. 413–419, 2014.
View at: Publisher Site | Google Scholar
L. Popescu, N. N. Gaudreault, K. M. Whitworth et al., “Genetically edited pigs lacking CD163 show no resistance following infection with the African swine fever virus isolate, Georgia 2007/1,” Virology, vol. 501, pp. 102–106, 2017.
View at: Publisher Site | Google Scholar
C. Sánchez-Torres, P. Gómez-Puertas, M. Gómez-del-Moral et al., “Expression of porcine CD163 on monocytes/macrophages correlates with permissiveness to African swine fever infection,” Archives of Virology, vol. 148, no. 12, pp. 2307–2323, 2003.
View at: Publisher Site | Google Scholar
M. A. Cuesta-Geijo, I. Galindo, B. Hernáez et al., “Endosomal maturation, Rab7 GTPase and phosphoinositides in African swine fever virus entry,” PLOS ONE, vol. 7, no. 11, Article ID e48853, 2012.
View at: Publisher Site | Google Scholar
B. Hernáez, M. Guerra, M. L. Salas, and G. Andrés, “African swine fever virus undergoes outer envelope disruption, capsid disassembly and inner envelope fusion before core release from multivesicular endosomes,” PLOS Pathogens, vol. 12, no. 4, Article ID e1005595, 2016.
View at: Publisher Site | Google Scholar
D. Gao, J. Wu, Y.-T. Wu et al., “Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses,” Science, vol. 341, no. 6148, pp. 903–906, 2013.
View at: Publisher Site | Google Scholar
M. Shang, K. Lu, W. Guan, S. Cao, M. Ren, and C. Zhou, “2^′,3^′-Cyclic GMP-AMP dinucleotides for STING-mediated immune modulation: principles, immunotherapeutic potential, and synthesis,” ChemMedChem, vol. 17, no. 2, Article ID e202100671, 2022.
View at: Publisher Site | Google Scholar
Q. Zhang, C. Chen, B. Xia, and P. Xu, “Chemical regulation of the cGAS-STING pathway,” Current Opinion in Chemical Biology, vol. 69, Article ID 102170, 2022.
View at: Publisher Site | Google Scholar
J. R. Schoenborn and C. B. Wilson, “Regulation of interferon-γ during innate and adaptive immune responses,” Tumor Immunology, vol. 96, pp. 41–101, 2007.
View at: Publisher Site | Google Scholar
J. Wei, W. Guo, H. Lian et al., “SNX8 mediates IFNγ-triggered noncanonical signaling pathway and host defense against Listeria monocytogenes,” Proceedings of the National Academy of Sciences, vol. 114, no. 49, pp. 13000–13005, 2017.
View at: Publisher Site | Google Scholar
H. You, S. Zheng, Z. Huang et al., “Herpes simplex virus 1 tegument protein UL46 inhibits TANK-binding kinase 1-mediated signaling,” mBio, vol. 10, no. 3, 2019.
View at: Publisher Site | Google Scholar
C. Zheng, “Protein dynamics in cytosolic DNA-sensing antiviral innate immune signaling pathways,” Frontiers in Immunology, vol. 11, Article ID 1255, 2020.
View at: Publisher Site | Google Scholar
W. M. Schneider, M. D. Chevillotte, and C. M. Rice, “Interferon-stimulated genes: a complex web of host defenses,” Annual Review of Immunology, vol. 32, no. 1, pp. 513–545, 2014.
View at: Publisher Site | Google Scholar
C. R. Bolen, S. Ding, M. D. Robek, and S. H. Kleinstein, “Dynamic expression profiling of type I and type III interferon-stimulated hepatocytes reveals a stable hierarchy of gene expression,” Hepatology, vol. 59, no. 4, pp. 1262–1272, 2014.
View at: Publisher Site | Google Scholar
S. Lukhele, G. M. Boukhaled, and D. G. Brooks, “Type I interferon signaling, regulation and gene stimulation in chronic virus infection,” Seminars in Immunology, vol. 43, Article ID 101277, 2019.
View at: Publisher Site | Google Scholar
A. M. V. Murthy, N. Robinson, and S. Kumar, “Crosstalk between cGAS–STING signaling and cell death,” Cell Death & Differentiation, vol. 27, no. 11, pp. 2989–3003, 2020.
View at: Publisher Site | Google Scholar
Y. Xiong, Y.-D. Tang, and C. Zheng, “The crosstalk between the caspase family and the cGAS‒STING signaling pathway,” Journal of Molecular Cell Biology, vol. 13, no. 10, pp. 739–747, 2021.
View at: Publisher Site | Google Scholar
Y. Xu, C. Chen, Z. Liao, and P. Xu, “cGAS-STING signaling in cell death: Mechanisms of action and implications in pathologies,” European Journal of Immunology, vol. 53, no. 9, Article ID e2350386, 2023.
View at: Publisher Site | Google Scholar
K. Wang, L. Ni, S. Wang, C. Zheng, and L. Hutt-Fletcher, “Herpes simplex virus 1 protein kinase US3 hyperphosphorylates p65/RelA and dampens NF-κB activation,” Journal of Virology, vol. 88, no. 14, pp. 7941–7951, 2014.
View at: Publisher Site | Google Scholar
J. Zhan, J. Wang, Y. Liang et al., “Apoptosis dysfunction: unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses,” Cell Communication and Signaling, vol. 22, no. 1, Article ID 149, 2024.
View at: Publisher Site | Google Scholar
S. Dedoni, M. C. Olianas, and P. Onali, “Interferon-β induces apoptosis in human SH-SY5Y neuroblastoma cells through activation of JAK–STAT signaling and down-regulation of PI3K/Akt pathway,” Journal of Neurochemistry, vol. 115, no. 6, pp. 1421–1433, 2010.
View at: Publisher Site | Google Scholar
A. Makowska, L. Wahab, T. Braunschweig et al., “Interferon beta induces apoptosis in nasopharyngeal carcinoma cells via the TRAIL-signaling pathway,” Oncotarget, vol. 9, no. 18, pp. 14228–14250, 2018.
View at: Publisher Site | Google Scholar
D. Goubau, R. Romieu-Mourez, M. Solis et al., “Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7,” European Journal of Immunology, vol. 39, no. 2, pp. 527–540, 2009.
View at: Publisher Site | Google Scholar
Q. Guo, D. Zhu, Y. Wang et al., “Targeting STING attenuates ROS induced intervertebral disc degeneration,” Osteoarthritis and Cartilage, vol. 29, no. 8, pp. 1213–1224, 2021.
View at: Publisher Site | Google Scholar
J. Petrasek, A. Iracheta-Vellve, T. Csak et al., “STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease,” Proceedings of the National Academy of Sciences, vol. 110, no. 41, pp. 16544–16549, 2013.
View at: Publisher Site | Google Scholar
Y. Tian, Z. Bao, Y. Ji, X. Mei, and H. Yang, “Epigallocatechin-3-gallate protects H₂O₂-induced nucleus pulposus cell apoptosis and inflammation by inhibiting cGAS/Sting/NLRP3 activation,” Drug Des Devel Ther, vol. 14, pp. 2113–2122, 2020.
View at: Publisher Site | Google Scholar
K. Tsuchiya, “Inflammasome-associated cell death: pyroptosis, apoptosis, and physiological implications,” Microbiology and Immunology, vol. 64, no. 4, pp. 252–269, 2020.
View at: Publisher Site | Google Scholar
M. M. Gaidt, T. S. Ebert, D. Chauhan et al., “The DNA Inflammasome in human myeloid cells is initiated by a STING-cell death program upstream of NLRP3,” Cell, vol. 171, no. 5, pp. 1110–1124.e18, 2017.
View at: Publisher Site | Google Scholar
J. Sarhan, B. C. Liu, H. I. Muendlein et al., “Constitutive interferon signaling maintains critical threshold of MLKL expression to license necroptosis,” Cell Death & Differentiation, vol. 26, no. 2, pp. 332–347, 2019.
View at: Publisher Site | Google Scholar
D. Chen, J. Tong, L. Yang et al., “PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors,” Proceedings of the National Academy of Sciences, vol. 115, no. 15, pp. 3930–3935, 2018.
View at: Publisher Site | Google Scholar
M. Jia, D. Qin, C. Zhao et al., “Redox homeostasis maintained by GPX4 facilitates STING activation,” Nature Immunology, vol. 21, no. 7, pp. 727–735, 2020.
View at: Publisher Site | Google Scholar
C. Li, Y. Zhang, J. Liu, R. Kang, D. J. Klionsky, and D. Tang, “Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death,” Autophagy, vol. 17, no. 4, pp. 948–960, 2021.
View at: Publisher Site | Google Scholar
I. Amador-Martinez, O. E. Aparicio-Trejo, B. Bernabe-Yepes et al., “Mitochondrial impairment: a link for inflammatory responses activation in the cardiorenal syndrome type 4,” International Journal of Molecular Sciences, vol. 24, no. 21, Article ID 15875, 2023.
View at: Publisher Site | Google Scholar
E. M. Mejia and G. M. Hatch, “Mitochondrial phospholipids: role in mitochondrial function,” Journal of Bioenergetics and Biomembranes, vol. 48, no. 2, pp. 99–112, 2016.
View at: Publisher Site | Google Scholar
A. K. Aranda-Rivera, A. Cruz-Gregorio, O. E. Aparicio-Trejo, and J. Pedraza-Chaverri, “Mitochondrial redox signaling and oxidative stress in kidney diseases,” Biomolecules, vol. 11, no. 8, Article ID 1144, 2021.
View at: Publisher Site | Google Scholar
A. Y. Andreyev, Y. E. Kushnareva, and A. A. Starkov, “Mitochondrial metabolism of reactive oxygen species,” Biochemistry, vol. 70, no. 2, pp. 200–214, 2005.
View at: Publisher Site | Google Scholar
M. Schieber and N. S. Chandel, “ROS function in redox signaling and oxidative stress,” Current Biology, vol. 24, no. 10, pp. R453–R462, 2014.
View at: Publisher Site | Google Scholar
H. Sies, V. V. Belousov, N. S. Chandel et al., “Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology,” Nature Reviews Molecular Cell Biology, vol. 23, no. 7, pp. 499–515, 2022.
View at: Publisher Site | Google Scholar
A. Peña-Blanco and A. J. García-Sáez, “Bax, bak and beyond—mitochondrial performance in apoptosis,” The FEBS Journal, vol. 285, no. 3, pp. 416–431, 2018.
View at: Publisher Site | Google Scholar
C.-H. Yu, S. Davidson, C. R. Harapas et al., “TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS,” Cell, vol. 183, no. 3, pp. 636–649.e18, 2020.
View at: Publisher Site | Google Scholar
K. Cosentino, V. Hertlein, A. Jenner et al., “The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation,” Molecular Cell, vol. 82, no. 5, pp. 933–949.e9, 2022.
View at: Publisher Site | Google Scholar
P. Gómez-Puertas, F. Rodríguez, J. M. Oviedo et al., “Neutralizing antibodies to different proteins of African swine fever virus inhibit both virus attachment and internalization,” Journal of Virology, vol. 70, no. 8, pp. 5689–5694, 1996.
View at: Publisher Site | Google Scholar
M. E. Heimerman, M. V. Murgia, P. Wu, A. D. Lowe, W. Jia, and R. R. Rowland, “Linear epitopes in African swine fever virus p72 recognized by monoclonal antibodies prepared against baculovirus-expressed antigen,” Journal of Veterinary Diagnostic Investigation, vol. 30, no. 3, pp. 406–412, 2018.
View at: Publisher Site | Google Scholar
D. Yin, R. Geng, H. Shao et al., “Identification of novel linear epitopes in P72 protein of African swine fever virus recognized by monoclonal antibodies,” Frontiers in Microbiology, vol. 13, Article ID 1055820, 2022.
View at: Publisher Site | Google Scholar
Z. Weng, X. Zheng, Y. Liang et al., “Porcine alveolar macrophages host proteins interacting with African swine fever virus p72,” Frontiers in Microbiology, vol. 15, Article ID 1370417, 2024.
View at: Publisher Site | Google Scholar
H. Sun, M. Wu, Z. Zhang et al., “OAS1 suppresses African swine fever virus replication by recruiting TRIM21 to degrade viral major capsid protein,” Journal of Virology, vol. 97, no. 10, Article ID e0121723, 2023.
View at: Publisher Site | Google Scholar
Q. Wu, Y. Lei, Y. Zuo et al., “Interactome between ASFV and host immune pathway proteins,” mSystems, vol. 8, no. 6, Article ID e0047123, 2023.
View at: Publisher Site | Google Scholar
P. Jiao, S. Wang, W. Fan et al., “Recombinant porcine interferon cocktail delays the onset and lessens the severity of African swine fever,” Antiviral Research, vol. 215, Article ID 105644, 2023.
View at: Publisher Site | Google Scholar
H. Chen, Z. Wang, X. Gao et al., “ASFV pD345L protein negatively regulates NF-κB signalling by inhibiting IKK kinase activity,” Veterinary Research, vol. 53, no. 1, Article ID 32, 2022.
View at: Publisher Site | Google Scholar
V. O’Donnell, G. R. Risatti, L. G. Holinka et al., “Simultaneous deletion of the 9GL and UK genes from the African swine fever virus Georgia 2007 isolate offers increased safety and protection against homologous challenge,” Journal of Virology, vol. 91, no. 1, Article ID e01760-16, 2017.
View at: Publisher Site | Google Scholar
F. B. Freitas, G. Frouco, C. Martins, and F. Ferreira, “African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle,” Scientific Reports, vol. 8, no. 1, Article ID 3471, 2018.
View at: Publisher Site | Google Scholar
L. Dixon, P. Sánchez-Cordón, I. Galindo, and C. Alonso, “Investigations of pro- and anti-apoptotic factors affecting African swine fever virus replication and pathogenesis,” Viruses, vol. 9, no. 9, Article ID 241, 2017.
View at: Publisher Site | Google Scholar
M.-M. Hu and H.-B. Shu, “Cytoplasmic mechanisms of recognition and defense of microbial nucleic acids,” Annual Review of Cell and Developmental Biology, vol. 34, no. 1, pp. 357–379, 2018.
View at: Publisher Site | Google Scholar
Y. Revilla, D. Pérez-Núñez, and J. A. Richt, “African swine fever virus biology and vaccine approaches,” in Virus Structure and Assembly, vol. 100, pp. 41–74, Elsevier, 2018.
View at: Publisher Site | Google Scholar
A. E. Afe, Z. J. Shen, X. Guo, R. Zhou, and K. Li, “African swine fever virus interaction with host innate immune factors,” Viruses, vol. 15, no. 6, Article ID 1220, 2023.
View at: Publisher Site | Google Scholar
K. M. Dolata, G. Pei, C. L. Netherton, and A. Karger, “Functional landscape of African swine fever virus–host and virus–virus protein interactions,” Viruses, vol. 15, no. 8, Article ID 1634, 2023.
View at: Publisher Site | Google Scholar
S. Hao, X. Zheng, Y. Zhu et al., “African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation,” Frontiers in Immunology, vol. 14, Article ID 1186916, 2023.
View at: Publisher Site | Google Scholar
J. Hong, X. Chi, X. Yuan et al., “I226R protein of African swine fever virus is a suppressor of innate antiviral responses,” Viruses, vol. 14, no. 3, Article ID 575, 2022.
View at: Publisher Site | Google Scholar
N. Dodantenna, L. Ranathunga, W. A. G. Chathuranga et al., “African swine fever virus EP364R and C129R target cyclic GMP-AMP to inhibit the cGAS-STING signaling pathway,” Journal of Virology, vol. 96, no. 15, Article ID e0102222, 2022.
View at: Publisher Site | Google Scholar
L. Ranathunga, N. Dodantenna, J.-W. Cha et al., “African swine fever virus B175L inhibits the type I interferon pathway by targeting STING and 2^′3^′-cGAMP,” Journal of Virology, vol. 97, no. 11, Article ID e0079523, 2023.
View at: Publisher Site | Google Scholar
M. Cheng, M. M. Kanyema, Y. Sun et al., “African swine fever virus L83L negatively regulates the cGAS-STING-mediated IFN-I pathway by recruiting tollip to promote STING autophagic degradation,” Journal of Virology, vol. 97, no. 2, Article ID e0192322, 2023.
View at: Publisher Site | Google Scholar
D. Li, W. Yang, L. Li et al., “African swine fever virus MGF-505-7R negatively regulates cGAS–STING-mediated signaling pathway,” The Journal of Immunology, vol. 206, no. 8, pp. 1844–1857, 2021.
View at: Publisher Site | Google Scholar
Y. Liu, W. Yang, Y. Wen et al., “[The E248R protein of African swine fever virus inhibits the cGAS-STING-mediated innate immunity],” Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology, vol. 38, no. 5, pp. 1837–1846, 2022.
View at: Publisher Site | Google Scholar
K. Yang, Q. Huang, R. Wang et al., “African swine fever virus MGF505-11R inhibits type I interferon production by negatively regulating the cGAS-STING-mediated signaling pathway,” Veterinary Microbiology, vol. 263, Article ID 109265, 2021.
View at: Publisher Site | Google Scholar
W. Zheng, N. Xia, J. Zhang et al., “African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING,” Frontiers in Immunology, vol. 13, Article ID 941579, 2022.
View at: Publisher Site | Google Scholar
Z. Zhu, S. Li, C. Ma et al., “African swine fever virus E184L protein interacts with innate immune adaptor STING to block ifn production for viral replication and pathogenesis,” The Journal of Immunology, vol. 210, no. 4, pp. 442–458, 2023.
View at: Publisher Site | Google Scholar
Q. Chen, X. X. Wang, S. W. Jiang et al., “MGF360-12L of ASFV-SY18 is an immune-evasion protein that inhibitshost type I IFN, NF-κB, and JAK/STATpathways,” Polish Journal of Veterinary Sciences, vol. 26, no. 1, pp. 119–130, 2023.
View at: Publisher Site | Google Scholar
S. Cui, Y. Wang, X. Gao et al., “African swine fever virus M1249L protein antagonizes type I interferon production via suppressing phosphorylation of TBK1 and degrading IRF3,” Virus Research, vol. 319, Article ID 198872, 2022.
View at: Publisher Site | Google Scholar
L. Huang, W. Xu, H. Liu et al., “African swine fever virus pI215L negatively regulates cGAS-STING signaling pathway through recruiting RNF138 to inhibit K63-linked ubiquitination of TBK1,” The Journal of Immunology, vol. 207, no. 11, pp. 2754–2769, 2021.
View at: Publisher Site | Google Scholar
H. Li, X. Zheng, Y. Li et al., “African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction,” Virologica Sinica, vol. 38, no. 6, pp. 911–921, 2023.
View at: Publisher Site | Google Scholar
Y. Li, L. Huang, H. Li et al., “ASFV pA151R negatively regulates type I IFN production via degrading E3 ligase TRAF6,” Frontiers in Immunology, vol. 15, Article ID 1339510, 2024.
View at: Publisher Site | Google Scholar
J. Luo, J. Zhang, J. Ni et al., “The African swine fever virus protease pS273R inhibits DNA sensing cGAS-STING pathway by targeting IKKepsilon,” Virulence, vol. 13, no. 1, pp. 740–756, 2022.
View at: Publisher Site | Google Scholar
J. Ren, D. Li, G. Zhu et al., “Deletion of MGF-110-9L gene from African swine fever virus weakens autophagic degradation of TBK1 as a mechanism for enhancing type I interferon production,” The FASEB Journal, vol. 37, no. 6, Article ID e22934, 2023.
View at: Publisher Site | Google Scholar
M. Sun, S. Yu, H. Ge et al., “The A137R protein of African swine fever virus inhibits type I interferon production via the autophagy-mediated lysosomal degradation of TBK1,” Journal of Virology, vol. 96, no. 9, Article ID e0195721, 2022.
View at: Publisher Site | Google Scholar
X. Wang, J. Wu, Y. Wu et al., “Inhibition of cGAS-STING-TBK1 signaling pathway by DP96R of ASFV China 2018/1,” Biochemical and Biophysical Research Communications, vol. 506, no. 3, pp. 437–443, 2018.
View at: Publisher Site | Google Scholar
K. Yang, Y. Xue, H. Niu et al., “African swine fever virus MGF360-11L negatively regulates cGAS-STING-mediated inhibition of type I interferon production,” Veterinary Research, vol. 53, no. 1, Article ID 7, 2022.
View at: Publisher Site | Google Scholar
G. Zhu, J. Ren, D. Li et al., “Combinational deletions of MGF110-9L and MGF505-7R genes from the African swine fever virus inhibit TBK1 degradation by an autophagy activator PIK3C2B to promote type I interferon production,” Journal of Virology, vol. 97, no. 5, Article ID e0022823, 2023.
View at: Publisher Site | Google Scholar
N. Dodantenna, J. W. Cha, K. Chathuranga et al., “The African swine fever virus virulence determinant DP96R suppresses type I IFN production targeting IRF3,” International Journal of Molecular Sciences, vol. 25, no. 4, Article ID 2099, 2024.
View at: Publisher Site | Google Scholar
H. Liu, Z. Zhu, T. Feng et al., “African swine fever virus E120R protein inhibits interferon beta production by interacting with IRF3 To block its activation,” Journal of Virology, vol. 95, no. 18, Article ID e0082421, 2021.
View at: Publisher Site | Google Scholar
X. Liu, H. Liu, G. Ye et al., “African swine fever virus pE301R negatively regulates cGAS-STING signaling pathway by inhibiting the nuclear translocation of IRF3,” Veterinary Microbiology, vol. 274, Article ID 109556, 2022.
View at: Publisher Site | Google Scholar
Y. Wang, S. Cui, T. Xin et al., “African swine fever virus MGF360-14L negatively regulates type I interferon signaling by targeting IRF3,” Frontiers in Cellular and Infection Microbiology, vol. 11, Article ID 818969, 2022.
View at: Publisher Site | Google Scholar
K. Zhang, H. Ge, P. Zhou et al., “The D129L protein of African swine fever virus interferes with the binding of transcriptional coactivator p300 and IRF3 to prevent beta interferon induction,” Journal of Virology, vol. 97, no. 10, Article ID e0082423, 2023.
View at: Publisher Site | Google Scholar
P. Gao, M. Ascano, Y. Wu et al., “Cyclic [G(2^′,5^′)pA(3^′,5^′)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase,” Cell, vol. 153, no. 5, pp. 1094–1107, 2013.
View at: Publisher Site | Google Scholar
X. Zhang, X.-C. Bai, and Z. J. Chen, “Structures and mechanisms in the cGAS-STING innate immunity pathway,” Immunity, vol. 53, no. 1, pp. 43–53, 2020.
View at: Publisher Site | Google Scholar
J. Song, K. Li, T. Li et al., “Screening of PRRSV- and ASFV-encoded proteins involved in the inflammatory response using a porcine iGLuc reporter,” Journal of Virological Methods, vol. 285, Article ID 113958, 2020.
View at: Publisher Site | Google Scholar
H.-B. Shu and Y.-Y. Wang, “Adding to the STING,” Immunity, vol. 41, no. 6, pp. 871–873, 2014.
View at: Publisher Site | Google Scholar
J. Zhang, M.-M. Hu, Y.-Y. Wang, and H.-B. Shu, “TRIM32 protein modulates type I interferon induction and cellular antiviral response by targeting MITA/STING protein for K63-linked ubiquitination,” Journal of Biological Chemistry, vol. 287, no. 34, pp. 28646–28655, 2012.
View at: Publisher Site | Google Scholar
T. Cavlar, T. Deimling, A. Ablasser, K.-P. Hopfner, and V. Hornung, “Species-specific detection of the antiviral small-molecule compound CMA by STING,” The EMBO Journal, vol. 32, no. 10, pp. 1440–1450, 2013.
View at: Publisher Site | Google Scholar
K.-H. Chin, Z.-L. Tu, Y.-C. Su et al., “Novel c-di-GMP recognition modes of the mouse innate immune adaptor protein STING,” Acta Crystallographica Section D Biological Crystallography, vol. 69, no. 3, pp. 352–366, 2013.
View at: Publisher Site | Google Scholar
G. Ye, H. Liu, X. Liu et al., “African swine fever virus H240R protein inhibits the production of type I interferon through disrupting the oligomerization of STING,” Journal of Virology, vol. 97, no. 9, Article ID e0057723, 2023.
View at: Publisher Site | Google Scholar
K. Yang, Y. Xue, T. Niu et al., “African swine fever virus MGF505-7R protein interacted with IRF7and TBK1 to inhibit type I interferon production,” Virus Research, vol. 322, Article ID 198931, 2022.
View at: Publisher Site | Google Scholar
J. Li, J. Song, L. Kang et al., “pMGF505-7R determines pathogenicity of African swine fever virus infection by inhibiting IL-1β and type I IFN production,” PLOS Pathogens, vol. 17, no. 7, Article ID e1009733, 2021.
View at: Publisher Site | Google Scholar
M. V. Borca, E. Ramirez-Medina, E. Silva et al., “Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic eurasia strain,” Journal of Virology, vol. 94, no. 7, Article ID e02017-19, 2020.
View at: Publisher Site | Google Scholar
W. Chen, D. Zhao, X. He et al., “A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs,” Science China Life Sciences, vol. 63, no. 5, pp. 623–634, 2020.
View at: Publisher Site | Google Scholar
X.-M. Geng, Y.-M. Xi, X.-M. Huang et al., “Construction of and evaluation of the immune response to two recombinant pseudorabies viruses expressing the B119L and EP364R proteins of African swine fever virus,” Archives of Virology, vol. 169, no. 2, Article ID 22, 2024.
View at: Publisher Site | Google Scholar
L. V. Goulding, E. Kiss, L. Goatley, R. Vrancken, N. E. J. Goris, and L. Dixon, “In vitro and in vivo antiviral activity of nucleoside analogue cHPMPC against African swine fever virus replication,” Antiviral Research, vol. 208, p. 105433, 2022.
View at: Publisher Site | Google Scholar
W. Liu, H. Li, B. Liu et al., “A new vaccination regimen using adenovirus-vectored vaccine confers effective protection against African swine fever virus in swine,” Emerging Microbes & Infections, vol. 12, no. 2, Article ID 2233643, 2023.
View at: Publisher Site | Google Scholar
Y. Liu, Z. Xie, Y. Li et al., “Evaluation of an I177L gene-based five-gene-deleted African swine fever virus as a live attenuated vaccine in pigs,” Emerging Microbes & Infections, vol. 12, no. 1, Article ID 2148560, 2023.
View at: Publisher Site | Google Scholar
J. Wei, C. Liu, X. He et al., “Generation and characterization of recombinant pseudorabies virus delivering African swine fever virus CD2v and p54,” International Journal of Molecular Sciences, vol. 25, no. 1, Article ID 335, 2024.
View at: Publisher Site | Google Scholar
Z. Wang, J. Zhang, F. Li et al., “The attenuated African swine fever vaccine HLJ/18-7GD provides protection against emerging prevalent genotype II variants in China,” Emerging Microbes & Infections, vol. 13, no. 1, Article ID 2300464, 2024.
View at: Publisher Site | Google Scholar
A. Rathakrishnan, A. L. Reis, V. Petrovan et al., “A protective multiple gene-deleted African swine fever virus genotype II, Georgia 2007/1, expressing a modified non-haemadsorbing CD2v protein,” Emerging Microbes & Infections, vol. 12, no. 2, Article ID 2265661, 2023.
View at: Publisher Site | Google Scholar
Y. Kuchitsu, K. Mukai, R. Uematsu et al., “STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes,” Nature Cell Biology, vol. 25, no. 3, pp. 453–466, 2023.
View at: Publisher Site | Google Scholar
J. Wang, Y. Zhang, C. Liu et al., “Trivalent mRNA Vaccine against SARS-CoV-2 and Variants with Effective Immunization,” Molecular Pharmaceutics, vol. 20, no. 10, pp. 4971–4983, 2023.
View at: Publisher Site | Google Scholar
L. E. Wee, N. Tang, D. Pang et al., “Effectiveness of monovalent mRNA vaccines against omicron XBB infection in Singaporean children younger than 5 years,” JAMA Pediatrics, vol. 177, no. 12, pp. 1324–1331, 2023.
View at: Publisher Site | Google Scholar
K. Yau, P. Tam, C. T. Chan et al., “BNT162b2 versus mRNA-1273 third dose COVID-19 vaccine in patients with CKD and maintenance dialysis patients,” Clinical Journal of the American Society of Nephrology, vol. 19, no. 1, pp. 85–97, 2023.
View at: Publisher Site | Google Scholar
H. M. Gunter, S. Idrisoglu, S. Singh et al., “mRNA vaccine quality analysis using RNA sequencing,” Nature Communications, vol. 14, no. 1, Article ID 5663, 2023.
View at: Publisher Site | Google Scholar
D. D. Kang, H. Li, and Y. Dong, “Advancements of in vitro transcribed mRNA (IVT mRNA) to enable translation into the clinics,” Advanced Drug Delivery Reviews, vol. 199, Article ID 114961, 2023.
View at: Publisher Site | Google Scholar
A. W. Freyn, C. Atyeo, P. L. Earl et al., “An mpox virus mRNA-lipid nanoparticle vaccine confers protection against lethal orthopoxviral challenge,” Science Translational Medicine, vol. 15, no. 716, Article ID eadg3540, 2023.
View at: Publisher Site | Google Scholar
F. Hou, Y. Zhang, X. Liu et al., “mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge,” Nature Communications, vol. 14, no. 1, Article ID 5925, 2023.
View at: Publisher Site | Google Scholar
X. Yang, C. Hu, X. Yang et al., “Evaluation and comparison of immune responses induced by two Mpox mRNA vaccine candidates in mice,” Journal of Medical Virology, vol. 95, no. 10, Article ID e29140, 2023.
View at: Publisher Site | Google Scholar
J. Zeng, Y. Li, L. Jiang et al., “Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge,” Emerging Microbes & Infections, vol. 12, no. 1, Article ID 2204151, 2023.
View at: Publisher Site | Google Scholar
N. Zhang, X. Cheng, Y. Zhu et al., “Multi-valent mRNA vaccines against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity,” Science China Life Sciences, vol. 66, no. 10, pp. 2329–2341, 2023.
View at: Publisher Site | Google Scholar
R.-R. Zhang, Z.-J. Wang, Y.-L. Zhu et al., “Rational development of multicomponent mRNA vaccine candidates against mpox,” Emerging Microbes & Infections, vol. 12, no. 1, Article ID 2192815, 2023.
View at: Publisher Site | Google Scholar
Y. Xiang, M. Tian, J. Huang et al., “LMP2-mRNA lipid nanoparticle sensitizes EBV-related tumors to anti-PD-1 therapy by reversing T cell exhaustion,” Journal of Nanobiotechnology, vol. 21, no. 1, Article ID 324, 2023.
View at: Publisher Site | Google Scholar
G.-X. Zhao, G.-L. Bu, G.-F. Liu et al., “mRNA-based vaccines targeting the T-cell epitope-rich domain of epstein barr virus latent proteins elicit robust anti-tumor immunity in mice,” Advanced Science, vol. 10, no. 35, Article ID e2302116, 2023.
View at: Publisher Site | Google Scholar
J. K. Jancovich, D. Chapman, D. T. Hansen et al., “Immunization of pigs by DNA prime and recombinant vaccinia virus boost to identify and rank African swine fever virus immunogenic and protective proteins,” Journal of Virology, vol. 92, no. 8, Article ID e02219-17, 2018.
View at: Publisher Site | Google Scholar
X. Zhang, X. Guan, Q. Wang et al., “Identification of the p34 protein of African swine fever virus as a novel viral antigen with protection potential,” Viruses, vol. 16, no. 1, Article ID 38, 2024.
View at: Publisher Site | Google Scholar
R. Zhu, Y. Wang, H. Zhang et al., “Deletion of the B125R gene in the African swine fever virus SY18 strain leads to an A104R frameshift mutation slightly attenuating virulence in domestic pigs,” Virus Research, vol. 343, Article ID 199343, 2024.
View at: Publisher Site | Google Scholar
J. Yang, R. Zhu, Y. Zhang et al., “Deleting the C84L gene from the virulent African swine fever virus SY18 does not affect its replication in porcine primary macrophages but reduces its virulence in Swine,” Pathogens, vol. 13, no. 2, Article ID 103, 2024.
View at: Publisher Site | Google Scholar
J. Fan, J. Zhang, F. Wang et al., “Identification of L11L and L7L as virulence-related genes in the African swine fever virus genome,” Frontiers in Microbiology, vol. 15, Article ID 1345236, 2024.
View at: Publisher Site | Google Scholar
X. Qi, T. Feng, Z. Ma et al., “Deletion of DP148R, DP71L, and DP96R attenuates African swine fever virus, and the mutant strain confers complete protection against homologous challenges in pigs,” Journal of Virology, vol. 97, no. 4, Article ID e0024723, 2023.
View at: Publisher Site | Google Scholar
V. O’Donnell, L. G. Holinka, P. W. Krug et al., “African swine fever virus Georgia 2007 with a deletion of virulence-associated gene 9GL (B119L), when administered at low doses, leads to virus attenuation in swine and induces an effective protection against homologous challenge,” Journal of Virology, vol. 89, no. 16, pp. 8556–8566, 2015.
View at: Publisher Site | Google Scholar
J. Song, M. Wang, L. Zhou et al., “A novel conserved B-cell epitope in pB602L of African swine fever virus,” Applied Microbiology and Biotechnology, vol. 108, no. 1, Article ID 78, 2024.
View at: Publisher Site | Google Scholar
Y. Tian, C. Liang, J. Zhou et al., “Identification of a novel B-cell epitope of the African swine fever virus p34 protein and development of an indirect ELISA for the detection of serum antibodies,” Frontiers in Microbiology, vol. 14, Article ID 1308753, 2024.
View at: Publisher Site | Google Scholar
P. Tian, Z. Sun, M. Wang et al., “Identification of a novel linear B-cell epitope on the p30 protein of African swine fever virus using monoclonal antibodies,” Virus Research, vol. 341, Article ID 199328, 2024.
View at: Publisher Site | Google Scholar
Q. Chen, L. Liu, S. Guo et al., “Characterization of the monoclonal antibody and the immunodominant B-cell epitope of African swine fever virus pA104R by using mouse model,” Microbiology Spectrum, vol. 12, no. 3, Article ID e0140123, 2024.
View at: Publisher Site | Google Scholar
Y. Hu, A. Wang, W. Yan et al., “Identification of linear epitopes in the C-terminal region of ASFV p72 Protein,” Microorganisms, vol. 11, no. 12, Article ID 2846, 2023.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2024 Songbiao Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

113

Downloads

76

Citations

Transboundary and Emerging Diseases

When ASFV Infection Meets the cGAS-STING Signaling Pathway

Abstract

1. Introduction

2. Overview of ASFV

3. Overview of cGAS-STING Signaling Pathway

3.1. The cGAS-STING Signaling Pathway and Interferon

3.2. The cGAS-STING Signaling Pathway and Cell Death

3.3. The cGAS-STING Signaling Pathway and Mitochondrial Dysfunction

4. Interaction between cGAS-STING Signaling Pathway and African Swine Fever Virus

4.1. Targeting cGAS Inhibits the Molecular Mechanism of cGAS-STING Activation

4.2. Targeting 2′,3′-cGAMP Inhibits the Molecular Mechanism of cGAS-STING Activation

4.3. Targeting STING Inhibits the Molecular Mechanism of cGAS-STING Activation

4.4. Targeting TBK1 Inhibits the Molecular Mechanism of cGAS-STING Activation

4.5. Targeting IRF3 Inhibits the Molecular Mechanism of cGAS-STING Activation

5. Conclusions and Perspectives

Conflicts of Interest

Authors’ Contributions

Acknowledgments

References

Copyright

4.2. Targeting 2^′,3^′-cGAMP Inhibits the Molecular Mechanism of cGAS-STING Activation