Flavivirus NS5 associates with host-cell proteins zonula occludens-1 (ZO-1) and regulating synaptic membrane exocytosis-2 (RIMS2) via an internal PDZ binding mechanism.
Dengue virus (DENV) and tick-borne encephalitis virus (TBEV) are flaviviruses, which can cause lethal hemorrhagic fever and encephalitis, respectively. Here, we demonstrate that the TBEV-NS5 and DENV-NS5 proteins use an internal binding mechanism to target human PDZ proteins. TBEV-NS5 has high affinity to regulating synaptic membrane exocytosis-2 (RIMS2) and Scribble, whereas DENV-NS5 binds primarily to the tight junction protein zonula occludens-1 (ZO-1). Targeting of TBEV-NS5 to the plasma membrane is stabilised by ZO-1; however, DENV-NS5 co-localises with ZO-1 in the nucleus. These interactions have potential important roles in the ability of flaviviruses to manipulate cell proliferation, junction permeability and the interferon pathways.
Ellencrona
Karin
K
School of Life Sciences, Södertörn University, S-14189 Huddinge, Sweden and Department of Genetics, Microbiology and Toxicology, Stockholm University, S-106 91, Stockholm, Sweden.
Syed
Asim
A
Johansson
Magnus
M
D000595:Amino Acid Sequence; D003716:Dengue Virus; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D054731:PDZ Domains; D010750:Phosphoproteins / Q000378:metabolism*; D016415:Sequence Alignment; D013570:Synaptic Membranes / Q000187:drug effects / Q000821:virology*; D019108:Tight Junctions; D017361:Viral Nonstructural Proteins / Q000378:metabolism* / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C096041:NS5 protein, flavivirus; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C485850:RIMS3 protein, human; C569042:TJP1 protein, human; D017361:Viral Nonstructural Proteins; D062826:Zonula Occludens-1 Protein