Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity

Scientific Reports
Emiliana M SilvaRonaldo Mohana-Borges

Abstract

Dengue is an important mosquito-borne disease and a global public health problem. The disease is caused by dengue virus (DENV), which is a member of the Flaviviridae family and contains a positive single-stranded RNA genome that encodes a single precursor polyprotein that is further cleaved into structural and non-structural proteins. Among these proteins, the non-structural 3 (NS3) protein is very important because it forms a non-covalent complex with the NS2B cofactor, thereby forming the functional viral protease. NS3 also contains a C-terminal ATPase/helicase domain that is essential for RNA replication. Here, we identified 47 NS3-interacting partners using the yeast two-hybrid system. Among those partners, we highlight several proteins involved in host energy metabolism, such as apolipoprotein H, aldolase B, cytochrome C oxidase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). GAPDH directly binds full-length NS3 and its isolated helicase and protease domains. Moreover, we observed an intense colocalization between the GAPDH and NS3 proteins in DENV2-infected Huh7.5.1 cells, in NS3-transfected BHK-21 cells and in hepatic tissue from a fatal dengue case. Taken together, these results suggest that the human GAPDH-DENV N...Continue Reading

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Citations

Jun 18, 2020·SAR and QSAR in Environmental Research·I KurniawanN Ikhsan
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kowit HengphasatpornThanyada Rungrotmongkol
Nov 25, 2020·Journal of Drug Targeting·Dana ElkhalifaAshraf Khalil
May 1, 2021·International Journal of Molecular Sciences·Xiaowen LiJinding Chen
Jul 24, 2021·European Journal of Medicinal Chemistry·Crystall SwarbrickGerasimos Rassias

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Methods Mentioned

BETA
two-hybrid
ELISA
surface plasmon resonance
confocal microscopy
chip
Co-IP
coimmunoprecipitation
transfection
acetylation
PCR

Software Mentioned

InterProSurf Protein - Protein Interaction Server
Prism
BLASTX
LAS AF Lite
BLASTN
ClusPro
PyMOL
PROCHECK
PSIPRED
MODELLER

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