Journal
BIOLOGICAL CHEMISTRY
Volume 390, Issue 4, Pages 319-323Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/BC.2009.041
Keywords
Dengue virus (DENV); flavivirus; PDZ domains; RIMS2; tick-borne encephalitis virus (TBEV); ZO-1
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Funding
- Swedish Research Council
- Baltic Sea foundation
- Magn. Bergwalls foundation
- Carl Tryggers foundation
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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.
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