Molecular Pathogens 2024, Vol.15, No.4, 209-218 http://microbescipublisher.com/index.php/mp 213 increased levels of chemokines such as CCL2, CCL5, and CXCL10 during acute ASFV infections, which are associated with severe clinical manifestations like lymphoid depletion, hemorrhages, and edema (Franzoni et al., 2023). 5 Viral Strategies for Immune System Evasion 5.1 Antigenic variation 5.1.1 Genetic mutations leading to variability African swine fever virus (ASFV) employs genetic mutations to create variability in its genome, which helps it evade the host immune system. Studies have shown that specific genes, such as EP402R and MGF505-2R, exhibit genetic diversity among different ASFV isolates. This variability is crucial for the virus's ability to modulate interferon production and the hemadsorption phenomenon, which are key aspects of its immune evasion strategy. The slow molecular evolution of these genes suggests that ASFV can adapt to different host environments over time, further complicating efforts to control the virus (Frączyk et al., 2016). 5.1.2 Escape from neutralizing antibodies ASFV also evades the host immune system by escaping neutralizing antibodies. The virus achieves this by inducing the production of non-neutralizing antibodies, which do not effectively target the virus for destruction. This mechanism allows ASFV to persist in the host and continue its replication cycle without being neutralized by the host's immune response (Wang et al., 2022). Additionally, the virus inhibits antigen presentation, which is crucial for the activation of adaptive immune responses, thereby further evading detection and neutralization by the host's immune system (Wang et al., 2022). 5.2 Subversion of host immune surveillance ASFV has developed sophisticated mechanisms to subvert host immune surveillance. One of the primary strategies involves the inhibition of interferon (IFN) production. The virus encodes several proteins, such as MGF360-14L and E184L, that target key components of the IFN signaling pathway. MGF360-14L promotes the degradation of IRF3, a critical transcription factor for IFN production, thereby inhibiting type I IFN signaling (Wang et al., 2022). Similarly, E184L interacts with the stimulator of IFN genes (STING) to block its signaling pathway, further reducing IFN production and impairing the host's antiviral response (Zhu et al., 2023). These strategies allow ASFV to evade the innate immune response, facilitating its replication and spread within the host (Zhu and Lin, 2024). 5.3 Manipulation of host cell signaling pathways ASFV manipulates host cell signaling pathways to create a favorable environment for its replication. The virus encodes multiple proteins that interfere with key signaling pathways involved in immune responses. For instance, the A238L protein inhibits NF-κB and nuclear activating factor in T-cells, which are essential for the activation of immune responses (Frączyk et al., 2016). Additionally, ASFV proteins such as L83L recruit cellular proteins like Tollip to promote the autophagic degradation of STING, thereby blocking the cGAS-STING-mediated IFN-I signaling pathway (Cheng et al., 2023). This manipulation of host cell signaling pathways not only helps the virus evade immune detection but also enhances its ability to replicate and cause disease. ASFV employs a multifaceted approach to evade the host immune system, including genetic mutations leading to antigenic variability, escape from neutralizing antibodies, subversion of host immune surveillance, and manipulation of host cell signaling pathways. These strategies collectively contribute to the virus's ability to persist in the host and cause severe disease outbreaks. 6 Challenges in Studying ASFV Immune Evasion 6.1 Technical and methodological challenges Studying the immune evasion mechanisms of African Swine Fever Virus (ASFV) presents several technical and methodological challenges. One significant hurdle is the complexity of the ASFV genome, which encodes numerous genes involved in immune modulation and evasion. For instance, the ASFV genome includes genes that
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