The Nuclear Pore Complex Is a Key Target of Viral Proteases to Promote Viral Replication

Figures

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  Figure 1. The machinery of the Nuclear Pore Complex. The NPC’s different components, which participate in the import and export of proteins and RNAs, and the FG-Nups, which participate in nuclear–cytoplasmic transport, are shown.

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  Figure 2. Bidirectional Nucleus–cytoplasm Transport. In the classical pathway of import (importin α/β), the importins and cargo complex are formed through the recognition of the NLS (nuclear location sequence). In the case of Export via CRM-1, the charge contains an NES (nuclear export sequence). In both cases, a GTP gradient is required. Molecules <40 kDa pass through passive diffusion towards the nucleus by the NPC.

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  Figure 3. Proteolytic targets of Flavivirus NS3. Panel (A) shows the Flavivirus RNA genomic organization encoding three structural and seven non-structural proteins. Panel (B) shows the NS3 from DENV-4 (Protease and Helicase in New Cartoon (helix-α in purple, 310 helix in blue, β-sheets in yellow, β-bridge in tan, and turn in cyan), and the zoom of the catalytic triad H51, D75, and S135 in green)). Also, cofactor NS2B (red) is shown (PDB ID: 2VBC). Panel (C) shows the cleavages of Nups by NS3pro from DENV and ZIKV.

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  Figure 4. Polyprotein cleavage and structure of Enterovirus 2Apro and 3Cpro. Panel (A) shows the Enterovirus RNA genome that encodes four structural and seven non-structural proteins and the cleavage sites by 2Apro and 3Cpro. Panel (B) shows 2Apro and its catalytic triad H18, D34, and C105, from RV (PDB ID: 2M5T). Panel (C) shows 3Cpro and its catalytic triad H40, E71, and C147, from PV (PDB ID: 1L1N). Color code: helix-α in purple, 310 helix in blue, β-sheets in yellow, β-bridge in tan, and turn in cyan.

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  Figure 5. NPC alterations by Poliovirus and Rhinovirus 2Apro and 3Cpro activity and cleavage consequences. Nups cleavages made up by 2Apro, and 3Cpro of RV and PV are shown. Some nuclear import and export pathways are shown in uninfected and RV and PV-infected cells. Inhibition of pathways of import and export nuclear are shown.