The non-structural 3 (NS3) protein of dengue virus type 2 interacts with human nuclear receptor binding protein and is associated with alterations in membrane structure

• Published in: Virus research 2004-06, Vol.102 (2), p.151-163
• Main Authors: Chua, John J.E., Ng, Mary M.L., Chow, Vincent T.K.
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cricetinae; Dengue pathogenesis; Dengue Virus - growth & development; Dengue Virus - metabolism; Dengue Virus - pathogenicity; Dengue virus type 2; Endoplasmic Reticulum, Rough - pathology; Endoplasmic Reticulum, Rough - virology; Intracellular Membranes - ultrastructure; Intracellular Membranes - virology; Membrane alterations; Microscopy, Confocal; Non-structural 3 protein; Nuclear receptor binding protein; Protein Binding; Protein Kinases - metabolism; Protein Transport; Protein-protein interactions; Receptors, Cytoplasmic and Nuclear - metabolism; RNA Helicases; Serine Endopeptidases; Two-Hybrid System Techniques; Vesicular Transport Proteins; Viral Nonstructural Proteins - metabolism; Virus Replication
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2004.01.025

Flaviviral infections produce a distinct array of virus-induced intracellular membrane alterations that are associated with the flaviviral replication machinery. Currently, it is still unknown which flaviviral protein(s) is/are responsible for this induction. Using yeast two-hybrid and co-immunoprecipitation analyses, we demonstrated that the NS3 protein of dengue virus type 2 interacted specifically with nuclear receptor binding protein (NRBP), a host cellular protein that influences trafficking between the endoplasmic reticulum (ER) and Golgi, and that interacts with Rac3, a member of the Rho-GTPase family. Co-expression of NS3 and NRBP in baby hamster kidney cells exhibited significant subcellular co-localization, and revealed the redistribution of NRBP from the cytoplasm to the perinuclear region. Furthermore, a set of membrane structures affiliated with the rough ER at the perinuclear region was induced in cells transfected with NS3. These structures are reminiscent of the virus-induced convoluted membranes previously observed in flavivirus-infected cells. This interaction between dengue viral and host cell proteins as well as the formation of the NS3-induced membrane structures suggest that NS3 may subvert the role of NRBP in ER-Golgi trafficking.