Genomics and Applied Biology 2024, Vol.15, No.5, 264-275 http://bioscipublisher.com/index.php/gab 268 5 Insights Gained from Gene Editing Studies 5.1 Understanding ASFV pathogenesis Gene editing tools, particularly CRISPR/Cas systems, have significantly advanced our understanding of African swine fever virus (ASFV) pathogenesis. By enabling precise manipulation of the ASFV genome, researchers have been able to identify and characterize the functions of various viral genes. For instance, the use of CRISPR/Cas9 has facilitated the identification of ASFV genes involved in immune evasion, such as those that inhibit the interferon response, which is crucial for the host's antiviral defense (Correia et al., 2013). Additionally, high-throughput proteomic analyses have revealed the interactome of key ASFV proteins, shedding light on the molecular pathways exploited by the virus during infection, such as intracellular and Golgi vesicle transport, endoplasmic reticulum organization, and lipid metabolism (García-Dorival et al., 2023) (Figure 2). These insights are pivotal for understanding the complex mechanisms of ASFV pathogenesis and identifying potential therapeutic targets. Figure 2 ASFV interactome significant hits related to Golgi transport and ER pathways (Adopted from García-Dorival et al., 2023) Image caption: ER membrane contacts are important in the control of membrane trafficking and regulation of intracellular organelles. ASFV interactome significant hits are highlighted in bold letters in the schematics. (A). Upon stress and high cholesterol content, endosomes and lysosomes move to a perinuclear location clustered around the microtubule-organizing center together with vesicles of the trans-Golgi network (TGN). This movement is orchestrated by ER VAP that regulates the association (or dissociation) of ORP1L, in complex with RILP, Rab7, and ORP1L and the HOPS complex through microtubule motor dynein, as shown in panel (A). (B). Lipid transfer proteins regulate cholesterol transfer between ER and Golgi membranes, mediated by SACM1, OSBP and VAP. SACM1 is an ER-resident phosphatase that dephosphorylates PtdIns4P in the ER. It is also regulated by the carnitine palmitoyltransferase (CPT) (Adopted from García-Dorival et al., 2023)
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