Molecular Pathogens 2024, Vol.15, No.4, 209-218 http://microbescipublisher.com/index.php/mp 210 disease known as African swine fever (ASF) (Zhu et al., 2019; Wu et al., 2021). The ASFV genome encodes numerous genes, some of which are not essential for virus replication but play crucial roles in modulating the host immune response and facilitating immune evasion (Gallardo et al., 2018). Key genes involved in immune evasion include those encoding proteins that inhibit interferon production, such as the multigene family protein MGF505-2R, and those that modulate host defense mechanisms, such as the CD2v lectin-like protein encoded by EP402R and EP153R genes (Frączyk et al., 2016). 2.2 Host immune response to ASFV Infection The host immune response to ASFV infection is multifaceted, involving both innate and adaptive immune mechanisms. Upon infection, ASFV primarily targets monocytes and macrophages, leading to significant alterations in cytokine production and immune signaling pathways (Zhu et al., 2019; He et al., 2022). The virus has developed several strategies to evade the host immune response, including: 1. Inhibition of Interferon Production: ASFV proteins such as MGF505-2R and A238L inhibit the production of type I interferons, which are critical for antiviral defense (Frączyk et al., 2016; Gallardo et al., 2018). This inhibition allows the virus to replicate efficiently within host cells without being detected by the immune system. 2. Modulation of Inflammatory Responses: ASFV infection leads to the upregulation of proinflammatory cytokines like IL-17F and interferons, while downregulating anti-inflammatory cytokines such as IL-10. This dysregulation contributes to excessive tissue inflammation and pathogenesis (Zhu et al., 2019; Ju et al., 2021). Additionally, ASFV proteins like pH240R inhibit the activation of the NLRP3 inflammasome, further dampening the host's inflammatory response (Huang et al., 2023). 3. Evasion of Antigen Presentation: ASFV interferes with the major histocompatibility complex (MHC) class II antigen processing and presentation, thereby avoiding detection by CD8+ T cells. This is achieved through the downregulation of chemokines that recruit neutrophils and CD8+ T effector cells (Zhu et al., 2019; Wang et al., 2022). 4. Inhibition of Apoptosis and Autophagy: ASFV encodes several apoptosis inhibitors, such as A224L, which prevent the programmed cell death of infected cells, allowing the virus to persist and replicate (Gallardo et al., 2018; Dixon et al., 2019). The virus also inhibits macrophage autophagy, a process that would otherwise help in clearing the infection (Zhu et al., 2019). 5. Regulation of Host Gene Expression: Transcriptome analyses have shown that ASFV infection leads to significant changes in host gene expression, including the suppression of immune-related genes and the enhancement of chemokine-mediated signaling pathways (Ju et al., 2021). These changes facilitate viral replication and spread while evading the host immune response. The complex interplay between ASFV and the host immune system highlights the virus's ability to manipulate host defenses to its advantage, making it a formidable pathogen in swine populations. Understanding these mechanisms is crucial for developing effective vaccines and therapeutic strategies against ASF. 3 Mechanisms of immune evasion 3.1 Inhibition of type I interferon response African Swine Fever Virus (ASFV) employs multiple strategies to inhibit the host's type I interferon (IFN) response, a critical component of the innate immune system. These strategies include interference with interferon signaling pathways, downregulation of interferon-stimulated genes, and the involvement of specific viral proteins in IFN inhibition. 3.1.1 Interference with interferon signaling pathways ASFV proteins such as MGF505-7R and pA104R have been shown to interfere with the Janus-activated kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. MGF505-7R inhibits the formation of the interferon-stimulated gene factor 3 (ISGF3) heterotrimer by interacting with interferon regulatory
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