Molecular Pathogens 2024, Vol.15, No.4, 209-218 http://microbescipublisher.com/index.php/mp 211 factor 9 (IRF9), thereby preventing its nuclear translocation and subsequent activation of IFN-stimulated response elements (ISRE) (Huang et al., 2023). Similarly, pA104R attenuates STAT1 phosphorylation, which is crucial for the activation of the IFN signaling cascade (Chen et al., 2023). 3.1.2 Downregulation of interferon-stimulated genes ASFV also downregulates the expression of interferon-stimulated genes (ISGs) through various mechanisms. The A137R protein of ASFV promotes the autophagy-mediated lysosomal degradation of TANK-binding kinase 1 (TBK1), thereby blocking the nuclear translocation of IRF3 and reducing type I IFN production (Sun et al., 2022). Additionally, MGF360-14L facilitates the degradation of IRF3 through ubiquitin-mediated proteolysis, further inhibiting IFN-β promoter activity (Wang et al., 2022). 3.1.3 Viral proteins involved in interferon inhibition Several ASFV-encoded proteins play direct roles in inhibiting type I IFN responses. For instance, the pI215L protein targets IRF9 for autophagic degradation, impairing the formation and nuclear translocation of ISGF3 (Li et al., 2022). The B175L protein inhibits the DNA virus-induced IFN-β production by targeting STING and 2'3'-cyclic GMP-AMP (cGAMP), essential components of the cGAS-STING signaling pathway (Ranathunga et al., 2023). Moreover, MGF360-12L blocks the interaction between importin α and the NF-κB signaling pathway, thereby inhibiting the nuclear localization of p50 and p65 and reducing IFN-β production (Zhuo et al., 2020). 3.2 Modulation of apoptosis ASFV encodes several proteins that modulate apoptosis, thereby aiding in immune evasion. These proteins inhibit apoptotic pathways, allowing the virus to persist within host cells. For example, ASFV proteins can inhibit the activation of caspases, which are crucial for the execution of apoptosis, thereby preventing the death of infected cells and allowing continued viral replication (Dixon et al., 2019). 3.3 Immune cell targeting and destruction ASFV primarily targets and replicates within macrophages and monocytes, key players in the host's immune response. By infecting these cells, ASFV disrupts their normal function and evades immune detection. The virus also employs strategies to inhibit the production of inflammatory cytokines and type I IFNs, further impairing the host's antiviral response (Liet al., 2021). This targeting and destruction of immune cells are critical for the virus's ability to evade the host's defenses and establish a successful infection. ASFV employs a multifaceted approach to evade the host's immune system, primarily through the inhibition of type I interferon responses, modulation of apoptosis, and targeting of immune cells. Understanding these mechanisms is crucial for developing effective vaccines and antiviral strategies against ASFV. 4 Modulation of the Host Inflammatory Response 4.1 Suppression of pro-inflammatory cytokines African swine fever virus (ASFV) employs several strategies to suppress the host's pro-inflammatory cytokine response, which is crucial for its immune evasion and pathogenesis. One of the key mechanisms involves the inhibition of transcription, maturation, and secretion of interleukin-1β (IL-1β) (Figure 1). The ASFV protein pH240R has been shown to target NF-κB signaling and impair NLRP3 inflammasome activation, leading to reduced IL-1β production. This suppression of IL-1β is significant because it helps the virus evade the host's antiviral inflammatory responses, thereby enhancing its virulence (Huang et al., 2023). Additionally, ASFV infection results in the down-regulation of several pro-inflammatory cytokines, including IL-17F and interferons, while simultaneously up-regulating anti-inflammatory cytokines like IL-10. This differential expression of cytokines contributes to the virus's ability to evade both innate and adaptive immune responses. For instance, the suppression of M1 macrophage activation and the inhibition of macrophage autophagy and apoptosis are critical for the virus to establish a successful infection (Zhu et al., 2019).
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