Attachment, Entry, and Intracellular Trafficking of Classical Swine Fever Virus

Figures

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  Figure 1. Basic features of CSFV and the organization of CSFV genome. (A) Schematic outline of a CSFV particle. CSFV is an enveloped, single-stranded, and positive-sense RNA virus. Three envelope proteins of CSFV-Erns, E1, and E2 are located on the external part of viral particles. As transmembrane proteins, E2 is present as homodimers or forms E1–E2 heterodimers on the virion. Unlike E1 buried underneath, Erns is exposed on the outside surface of the envelope with E2 and exists as a dimer. C proteins condense viral RNA genome with an unspecific affinity for nucleic acids. (B) Schematic organization of CSFV genome. The length of the genome is approximately 12.3 kb. The viral genome is composed of a large open reading frame (ORF), a 5’-noncoding region (5′-UTR), and a 3’-noncoding region (3’-UTR). The ORF encodes a precursor polyprotein, which is cleaved into four structural proteins (C, Erns, E1, and E2) and eight nonstructural proteins (Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B).

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  Figure 2. Model of CSFV entry and intracellular transport. The attachment to receptors (HS, LamR, CD46, MERTK, ADAM17, etc.) mediated by CSFV Erns or E2 facilitates penetration and entry ① The CSFV particles are endocytosed within clathrin-coated endosomes (in PK-15 cells) or internalized via a caveolae-dependent pathway (in 3D4/21 cells), followed by dynamin-mediated scission from the plasma membrane, during which actin cytoskeleton is required and ESCRT proteins (Tsg101, VPS25, CHMP4B, CHMP7, etc.) are involved. Clathrin interacts with Tsg101, CHMP4B, VPS25, and CHMP7 during CSFV entry, and is then transported to the EEs ②. Subsequently, CSFV transports from EEs to LEs along microfilaments with the assistance of Rabs, ESCRT proteins (Tsg101, CHMP4B, CHMP7), and other factors (GBF1, ARF1, COP I, VCP, etc.). Among them, Rab5 and Rab7 function in coordinating the transition from early to late endosomes. Rab9 participates in the migration of cargo between late endosomes and the trans-Golgi network, and Rab11 guides the transit to REs. In the EEs, VCP/CHMP4B/CHMP7 interact with Rab5 and assist in CSFV transportation to the LEs ③. In the LEs, Tsg101/CHMP7/CHMP4B interact with Rab9 and…