International Journal of Molecular Veterinary Research, 2024, Vol.14, No.5, 185-193 http://animalscipublisher.com/index.php/ijmvr 189 pathway by degrading STAT1 and STAT (Lv et al., 2022), thereby inhibiting interferon (IFN)-β signaling, which is essential for antiviral defense. The I267L gene further impairs the RNA polymerase III-RIG-I-mediated innate immune response, highlighting its role as a significant virulence factor (Ran et al., 2022; Zhang et al., 2022). 4.2 Interaction of ASFV with host apoptotic pathways ASFV has developed mechanisms to manipulate host apoptotic pathways to enhance its survival and replication. The A179L gene, a BCL-2 family protein, plays a pivotal role in inhibiting apoptosis by binding to pro-apoptotic proteins, thus preventing cell death and allowing prolonged virus replication. Interestingly, while A179L suppresses apoptosis, it enhances necroptosis, a form of programmed cell death, which may be a strategy to modulate host cell death pathways to the virus's advantage (Shi et al., 2021). The deletion of A179L results in increased apoptosis and reduced virus spread, indicating its critical role in ASFV virulence (Reis et al., 2023). 4.3 Case study: role of the A179L gene in ASFV virulence The A179L gene is a key player in ASFV's ability to evade host defenses and maintain virulence. Studies have shown that deletion of the A179L gene from the ASFV genome leads to increased apoptosis in infected macrophages, which in turn reduces virus replication and spread. This gene's role in suppressing apoptosis while enhancing necroptosis suggests a complex interaction with host cell death pathways, which may be exploited to develop attenuated vaccines (Shi et al., 2021). Pigs infected with an A179L-deleted virus showed reduced clinical symptoms and lower viremia, although they were not fully protected against subsequent challenges with the virulent parental virus, underscoring the gene's importance in ASFV pathogenicity (Reis et al., 2023). In summary, ASFV employs a range of molecular mechanisms to modulate host immune responses and apoptotic pathways, with genes like A238L, MGF360-9L, I267L, and A179L playing crucial roles in its virulence. Understanding these interactions provides insights into potential targets for vaccine development and therapeutic interventions. 5 Genetic Variation and Virulence 5.1 Genetic diversity across ASFV strains African swine fever virus (ASFV) exhibits significant genetic diversity, which is reflected in the variation of its virulence and pathogenicity across different strains. The ASFV genome is large and complex, encoding over 150 genes, many of which have not been fully characterized (Ramírez-Medina et al., 2022). This genetic diversity is evident in the differential expression of viral genes and the host's response to infection. For instance, a study comparing highly virulent and low virulent ASFV strains revealed distinct expression programs and host immune responses, highlighting the genetic variability among strains (Lv et al., 2022). Additionally, the deletion of specific virulence-associated genes, such as those in the multigene family (MGF), can lead to attenuated phenotypes, further illustrating the genetic diversity and its impact on virulence (Wang et al., 2023; Sun et al., 2024). 5.2 Influence of mutations on ASFV virulence Mutations in ASFV genes can significantly influence the virus's virulence. For example, the deletion of the A151R gene in the ASFV Georgia 2010 isolate resulted in a marked reduction in virulence, as pigs infected with the mutant strain exhibited lower virus titers and milder symptoms compared to those infected with the wild-type virus (Ramírez-Medina et al., 2022). Similarly, the deletion of the DP96R gene, which is involved in suppressing the host's interferon response, has been shown to attenuate the virus, although the precise molecular mechanisms remain to be fully elucidated (Ramírez-Medina et al., 2019; Dodantenna et al., 2024) 3. These findings underscore the critical role of specific genetic mutations in modulating ASFV virulence and highlight potential targets for vaccine development. 5.3 Genotype-specific virulence and pathogenicity ASFV strains exhibit genotype-specific differences in virulence and pathogenicity, which are influenced by the presence or absence of certain virulence genes. For instance, the I73R gene has been identified as a critical virulence factor, with its deletion leading to a significant reduction in pathogenicity, making it a potential target
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