PMID:22796133

Citation	Melik, W, Ellencrona, K, Wigerius, M, Hedström, C, Elväng, A and Johansson, M (2012) Two PDZ binding motifs within NS5 have roles in Tick-borne encephalitis virus replication. Virus Res. 169:54-62
Abstract	The flavivirus genus includes important human neurotropic pathogens like Tick-borne encephalitis virus (TBEV) and West-Nile virus (WNV). Flavivirus replication occurs at replication complexes, where the NS5 protein provides both RNA cap methyltransferase and RNA-dependent RNA polymerase activities. TBEVNS5 contains two PDZ binding motifs (PBMs) important for specific targeting of human PDZ proteins including Scribble, an association important for viral down regulation of cellular defense systems and neurite outgrowth. To determine whether the PBMs of TBEVNS5 affects virus replication we constructed a DNA based sub-genomic TBEV replicon expressing firefly luciferase. The PBMs within NS5 were mutated individually and in concert and the replicons were assayed in cell culture. Our results show that the replication rate was impaired in all mutants, which indicates that PDZ dependent host interactions influence TBEV replication. We also find that the C-terminal PBMs present in TBEVNS5 and WNVNS5 are targeting various human PDZ domain proteins. TBEVNS5 has affinity to Zonula occludens-2 (ZO-2), GIAP C-terminus interacting protein (GIPC), calcium/calmodulin-dependent serine protein kinase (CASK), glutamate receptor interacting protein 2, (GRIP2) and Interleukin 16 (IL-16). A different pattern was observed for WNVNS5 as it associate with a broader repertoire of putative host PDZ proteins.
Links	PubMed Online version:10.1016/j.virusres.2012.07.001
Keywords	Amino Acid Motifs; Animals; COS Cells; Cercopithecus aethiops; Encephalitis Viruses, Tick-Borne/pathogenicity; Encephalitis Viruses, Tick-Borne/physiology; Genes, Reporter; Host-Pathogen Interactions; Luciferases, Firefly/analysis; Luciferases, Firefly/genetics; Viral Nonstructural Proteins/metabolism; Virus Replication; West Nile virus/pathogenicity; West Nile virus/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
9FLAV:G4XII4		GO:0019079: viral genome replication	ECO:0000315:		P		Figure 2. Mutations is the NS5 protein in viral replication of Tick-borne encephalitis	complete CACAO 8674
9FLAV:G4XII4		GO:0019079: viral genome replication	ECO:0000314:		P		Figure 3B.Binding capacities of NS5 of Tick-borne encephalitis and West Nile virus encephalitis.	complete CACAO 8676
9FLAV:G4XII4	involved_in	GO:0019079: viral genome replication	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
9FLAV:G4XII4	involved_in	GO:0019079: viral genome replication	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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