PMID- 22796133
OWN - NLM
STAT- MEDLINE
DCOM- 20130227
LR  - 20191210
IS  - 1872-7492 (Electronic)
IS  - 0168-1702 (Linking)
VI  - 169
IP  - 1
DP  - 2012 Oct
TI  - Two PDZ binding motifs within NS5 have roles in Tick-borne encephalitis virus 
      replication.
PG  - 54-62
LID - S0168-1702(12)00247-X [pii]
LID - 10.1016/j.virusres.2012.07.001 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Melik, Wessam
AU  - Melik W
AD  - School of Life Sciences, Sodertorn University, S-141 89 Huddinge, Sweden.
FAU - Ellencrona, Karin
AU  - Ellencrona K
FAU - Wigerius, Michael
AU  - Wigerius M
FAU - Hedstrom, Christer
AU  - Hedstrom C
FAU - Elvang, Annelie
AU  - Elvang A
FAU - Johansson, Magnus
AU  - Johansson M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120710
PL  - Netherlands
TA  - Virus Res
JT  - Virus research
JID - 8410979
RN  - 0 (NS5 protein, flavivirus)
RN  - 0 (Viral Nonstructural Proteins)
RN  - EC 1.13.12.7 (Luciferases, Firefly)
SB  - IM
MH  - *Amino Acid Motifs
MH  - Animals
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Encephalitis Viruses, Tick-Borne/pathogenicity/*physiology
MH  - Genes, Reporter
MH  - *Host-Pathogen Interactions
MH  - Luciferases, Firefly/analysis/genetics
MH  - Viral Nonstructural Proteins/*metabolism
MH  - *Virus Replication
MH  - West Nile virus/pathogenicity/physiology
EDAT- 2012/07/17 06:00
MHDA- 2013/02/28 06:00
CRDT- 2012/07/17 06:00
PHST- 2012/03/02 00:00 [received]
PHST- 2012/07/02 00:00 [revised]
PHST- 2012/07/03 00:00 [accepted]
PHST- 2012/07/17 06:00 [entrez]
PHST- 2012/07/17 06:00 [pubmed]
PHST- 2013/02/28 06:00 [medline]
AID - S0168-1702(12)00247-X [pii]
AID - 10.1016/j.virusres.2012.07.001 [doi]
PST - ppublish
SO  - Virus Res. 2012 Oct;169(1):54-62. doi: 10.1016/j.virusres.2012.07.001. Epub 2012 
      Jul 10.