International Journal of Molecular Veterinary Research, 2024, Vol.14, No.5, 185-193 http://animalscipublisher.com/index.php/ijmvr 186 2 ASFV Genome and Molecular Biology 2.1 Structure and composition of ASFV genome The African swine fever virus (ASFV) is characterized by a large double-stranded DNA (dsDNA) genome, which encodes for more than 150 genes, many of which remain uncharacterized (Vuono et al., 2021; Ramírez-Medina et al., 2022; Ramírez-Medina et al., 2023). The genome is known to include various multigene families (MGFs) that play roles in viral replication and virulence (Wang t al., 2023). Specific genes such as A151R, E66L, and KP177R have been studied for their roles in the virus's structure and function, although not all are essential for replication in swine macrophages. The ASFV genome also contains AT-rich regions that are recognized by host immune sensors, indicating its complex interaction with host cellular mechanisms (Ran et al., 2022). 2.2 Replication mechanism of ASFV in host cells ASFV replicates primarily in swine macrophages, where it utilizes host cellular machinery to propagate. The replication process involves the transcription of viral genes, some of which, like E66L, are involved in arresting host gene transcription (Ramírez-Medina et al., 2023). The virus's ability to evade host immune responses is facilitated by proteins such as I267L, which inhibits RNA polymerase III-RIG-I-mediated innate immune responses, thereby enhancing viral replication and virulence (Ran et al., 2022). Additionally, the MGF300-2R protein promotes autophagic degradation of host proteins, further aiding in viral replication (Wang t al., 2023). 2.3 Molecular techniques for studying ASFV Molecular techniques such as the development of recombinant ASFV strains have been pivotal in studying the virus's replication and virulence. For instance, deletion mutants like ASFV-G-ΔA151R and ASFV-G-ΔE66L have been used to assess the roles of specific genes in replication and virulence (Ramírez-Medina et al., 2022; Ramírez-Medina et al., 2023). Transcriptome analysis using RNA-seq has also been employed to profile viral and host gene expression dynamics, providing insights into the molecular interactions during ASFV infection (Figure 1) (Lv et al., 2022). These techniques have been instrumental in identifying potential targets for vaccine development and understanding the virus's pathogenic mechanisms (Liu et al., 2023; Li et al., 2023). In summary, the ASFV genome is complex and encodes numerous genes that contribute to its virulence and replication. Understanding the structure, replication mechanisms, and molecular techniques used to study ASFV is crucial for developing effective control strategies against this devastating virus. 3 Virulence Factors of ASFV 3.1 Identification of key ASFV virulence genes African swine fever virus (ASFV) is a complex pathogen with a variety of genes contributing to its virulence. Key virulence genes include A238L, which regulates NFκB and NFAT, and A224L, an apoptosis inhibitor, both of which are involved in immune evasion (Gallardo et al., 2018). The I73R gene is another critical virulence-related gene, playing a significant role in down-regulating the host's natural immune response, making it a potential target for vaccine development (Figure 2) (Liu et al., 2023). Additionally, the I267L gene inhibits RNA polymerase III-RIG-I-mediated innate immune responses, further contributing to ASFV's virulence (Ran et al., 2022). 3.2 Mechanisms of immune evasion by ASFV ASFV employs several strategies to evade the host immune system. The virus can inhibit MHC Class II antigen processing and presentation, thereby avoiding detection by CD8+ T effector cells (Zhu et al., 2019). Proteins such as MGF360-9L and MGF360-10L play roles in immune evasion by degrading key signaling molecules like STAT1 and JAK1, respectively, which are crucial for the activation of interferon responses (Zhang et al., 2022; Li et al., 2023). The DP96R protein suppresses type I interferon production by targeting IRF3, further aiding in immune evasion (Dodantenna et al., 2024). 3.3 Contribution of ASFV structural proteins to pathogenesis ASFV structural proteins significantly contribute to its pathogenesis. The MGF300-2R protein promotes the autophagic degradation of IKKα and IKKβ, which are involved in inflammatory responses, thereby modulating
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