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- Brooks, Andrew J, et al.
(författare)
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The Interdomain Region of Dengue NS5 ProteinInteracts with NS3 and Host Proteins
- 2002
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Ingår i: Dengue Bulletin. - 1020-895X. ; 26, s. 155-161
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Although dengue virus genome replication occurs in the cytoplasm of infected cells, it has been shown that the NS5 protein (RNA-dependent RNA polymerase) is hyperphosphorylated at a late stage in infection and localized to the cell nucleus. A 37 amino acid sequence of NS5 (residues 369-405) was shown to contain a functional nuclear localization signal (NLS) that interacted with the cellular nuclear transport factor, importin α/β heterodimer. Further studies using the yeast two-hybrid system revealed that the NS5 region (residues 320-368) immediately adjacent to the NLS contained an importin β-binding site that abuts or overlaps the binding site for the NS3 protein (protease/helicase). The importin β-binding site has also been shown to be a functional NLS (bNLS). Intriguingly, when both bNLS and NLS (residues 320-405) were present, the fused β -galactosidase protein did not accumulate in the nucleus. Here we provide a review of our studies on the NS5 interdomain region and compare it to other members of the Flavivirus genus in order to highlight the importance of this region as a possible target for developing broad-acting antiviral agent against dengue and other mechanistically-related viruses.
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