Human Norovirus Proteins: Implications in the Replicative Cycle, Pathogenesis, and the Host Immune Response

Figures

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  Figure 1. Molecular structure of human norovirus (HuNoV). (A) A schematic representation of the human norovirus virion showing its 90-dimer protein surface of the VP1 structural protein of the capsid. The structural protein VP2 (1–8 proteins per virion) is shown within the viral capsid. The non-structural VPg protein, covalently bound to the 5′ end of the RNA genome (ssRNA+) in a positive sense and a poly-adenine tail at the 3′ ends are also displayed. (B) General scheme of the HuNoV genome organization. ORF1 encodes the non-structural proteins: p48, NTPase, p22, VPg, Protease, and RdRp. The ORF2 encodes for the major structural protein VP1 and the ORF3 encodes for the minor structural protein VP2. The subgenomic RNA bound to VPg encoding VP1 and VP2 is indicated below the ORFs. VPg is represented as a circle linked to genomic and subgenomic RNAs.

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  Figure 2. Model of a Replicative HuNoV Cycle and Function of its Proteins. (1) The replication process begins with the binding of the P2 region present in the P domain of VP1 to a still unknown receptor and some host co-receptors such as HBGA; (2, 3) After this union there is an internalization of the virus in the cell and a disassembly of the virus releasing the RNA in the cell cytoplasm; (4, 5) once in the cytoplasm, the covalently linked VPg protein at the 5′ end induces the binding of translation initiation factors, such as eIF3, and the binding of major and minor ribosomal subunits, producing genome translation viral thus generating a non-structural polyprotein, the VP1 protein, and the VP2 protein; (6) after this, the Pro protein cleaves the polyprotein generating three precursors, but only the Pro-Pol precursor has enzymatic activity, these precursors are subsequently cleaved generating the six individual proteins; (7) subsequently: (A) The P48 protein migrates to the reticulum and subsequently to the Golgi. (B) The NTPase protein will help in the replication process. (C) The P22 protein binds to the vesicles coated with COPII and contributes synergistically with the disassembly of…