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Two PDZ binding motifs within NS5 have roles in Tick-borne encephalitis virus replication
School of Life Sciences, Södertörn University, Huddinge, Sweden.
School of Life Sciences, Södertörn University, Huddinge, Sweden.
School of Life Sciences, Södertörn University, Huddinge, Sweden; Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax NS, Canada.
School of Life Sciences, Södertörn University, Huddinge, Sweden.
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2012 (English)In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 169, no 1, p. 54-62Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Amsterdam, Netherlands: Elsevier, 2012. Vol. 169, no 1, p. 54-62
Keywords [en]
Flaviviruses, tick-borne encephalitis virus replication, PDZ domains, NS5, replicon
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-27099DOI: 10.1016/j.virusres.2012.07.001ISI: 000311133800008PubMedID: 22796133Scopus ID: 2-s2.0-84867223730OAI: oai:DiVA.org:oru-27099DiVA, id: diva2:601442
Available from: 2013-01-29 Created: 2013-01-29 Last updated: 2018-05-10Bibliographically approved

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Johansson, Magnus

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