PMID:16033967

Citation	Hidajat, R, Nagano-Fujii, M, Deng, L, Tanaka, M, Takigawa, Y, Kitazawa, S and Hotta, H (2005) Hepatitis C virus NS3 protein interacts with ELKS-{delta} and ELKS-{alpha}, members of a novel protein family involved in intracellular transport and secretory pathways. J. Gen. Virol. 86:2197-208
Abstract	The NS3 protein of hepatitis C virus (HCV) has a serine protease activity in its N-terminal region, which plays a crucial role in virus replication. This region has also been reported to interact not only with its viral cofactor NS4A, but also with a number of host-cell proteins, which suggests a multifunctional feature of NS3. By means of yeast two-hybrid screening using an N-terminal region of NS3 as bait, a human cDNA encoding a region of ELKS-delta, a member of a novel family of proteins involved in intracellular transport and secretory pathways, was molecularly cloned. Using co-immunoprecipitation, GST pull-down and confocal and immunoelectron microscopic analyses, it was shown that full-length NS3 interacted physically with full-length ELKS-delta and its splice variant, ELKS-alpha, both in the absence and presence of NS4A, in cultured human cells, including Huh-7 cells harbouring an HCV subgenomic RNA replicon. The degree of binding to ELKS-delta varied with different sequences of the N-terminal 180 residues of NS3. Interestingly, NS3, either full-length or N-terminal fragments, enhanced secretion of secreted alkaline phosphatase (SEAP) from the cells, and the increase in SEAP secretion correlated well with the degree of binding between NS3 and ELKS-delta. Taken together, these results suggest the possibility that NS3 plays a role in modulating host-cell functions such as intracellular transport and secretion through its binding to ELKS-delta and ELKS-alpha, which may facilitate the virus life cycle and/or mediate the pathogenesis of HCV.
Links	PubMed Online version:10.1099/vir.0.80862-0
Keywords	Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Alkaline Phosphatase/metabolism; Amino Acid Sequence; Biological Transport; Cell Line, Tumor; DNA, Complementary; Hepacivirus/physiology; Hepatitis C/metabolism; Hepatitis C/virology; Humans; Membrane Proteins/metabolism; Molecular Sequence Data; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Protein Binding; Replicon; Sequence Alignment; Serine Endopeptidases/metabolism; Two-Hybrid System Techniques; Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/metabolism; Virus Replication
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HCVH:POLG	involved_in	GO:0010694: positive regulation of alkaline phosphatase activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HCVH:POLG	colocalizes_with	GO:0030430: host cell cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HCVH:POLG	colocalizes_with	GO:0044220: host cell perinuclear region of cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HCVH:POLG	involved_in	GO:0051047: positive regulation of secretion	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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