International Journal of Molecular Veterinary Research, 2024, Vol.14, No.6, 261-268 http://animalscipublisher.com/index.php/ijmvr 262 host cells via clathrin-mediated endocytosis (Figure 1) (Chen et al., 2023). This interaction is essential for the virus to attach and subsequently internalize into the host cell. The specific receptors and attachment factors involved in ASFV entry are still being studied, but CD1d has been identified as a significant host-entry factor. Figure 1 Schematic illustration of CD1d in enhancing ASFV endocytosis as a host factor (Adopted from Chen et al., 2023) Image caption: ASFV virions enter host cells via host factor CD1d on the cell membrane. The p72 on the surface of the ASFV virion binds with CD1d on the cell membrane. The signal is then transmitted to EPS15 in the cytoplasm to form the p72-CD1d-EPS15 axis, where CD1d recruits EPS15 through the interaction between CD1d and EPS15 intracellular domains. The process promotes the formation of EPS15-AP-2-clathrin complexes and aggregation, resulting in ASFV virions endocytosis during ASFV infection (Adopted from Chen et al., 2023) 2.2 Internalization and endosomal trafficking Once attached, ASFV enters host cells primarily through clathrin-mediated endocytosis, a process that is dynamin-dependent and requires cellular cholesterol (Galindo et al., 2015). ASFV can also utilize macropinocytosis, a form of endocytosis characterized by actin reorganization and membrane ruffling, to enter host cells (Sánchez et al., 2012). After internalization, ASFV traffics through the endolysosomal system, where it undergoes disassembly in acidic late endosomes, a process crucial for successful infection. The virus's internalization and trafficking are tightly regulated by host cell factors, including small GTPases and phosphoinositide signaling. 2.3 Escape to the cytoplasm The escape of ASFV to the cytoplasm involves the fusion of the viral membrane with endosomal membranes, a process facilitated by viral proteins such as pE199L. This protein is necessary for the fusion event that allows the viral core to penetrate the host cell cytoplasm, enabling the release of the viral genome. The uncoating process involves the loss of outer capsid layers and the fusion of the inner viral membrane with endosomes, which is essential for the virus to establish infection within the host cell (Sánchez et al., 2017). 3 ASFV-Host Interactions During Replication 3.1 Hijacking host transcriptional machinery African swine fever virus (ASFV) employs sophisticated mechanisms to manipulate host transcriptional machinery to favor its replication. ASFV regulates the activation of several transcription factors, thereby controlling the expression of specific target genes during infection (Sánchez et al., 2013). This regulation includes the compartmentalization of viral mRNA and ribosomes with cellular translation factors within the virus factory, which facilitates the preferential expression of viral genes over host genes. Additionally, ASFV infection leads to the dysregulation of host metabolism, which further promotes viral replication at the transcriptional level (Ju et al., 2021). 3.2 Manipulation of host immune responses ASFV has evolved multiple strategies to evade and manipulate host immune responses, ensuring its survival and replication. The virus interacts with host innate immune factors, inhibiting and inducing various signaling pathways such as cGAS-STING, NF-κB, and TGF-β (Figure 2) (Afe et al., 2023). ASFV also downregulates host immune-related genes and microRNAs that target viral genes, thereby suppressing the host's antiviral response.
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