TY - JOUR
T1 - Inhibition of N-myristoyltransferase1 affects dengue virus replication
AU - Suwanmanee, San
AU - Mahakhunkijcharoen, Yuvadee
AU - Ampawong, Sumate
AU - Leaungwutiwong, Pornsawan
AU - Missé, Dorothée
AU - Luplertlop, Natthanej
N1 - Publisher Copyright:
© 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Dengue virus (DENV) causes dengue fever, a self-limiting disease that could be fatal due to serious complications. No specific treatment is currently available and the preventative vaccine is only partially protective. To develop a potential drug target for dengue fever, we need to understand its biology and pathogenesis thoroughly. N-myristoyltransferase (NMT) is an N-terminal protein lipidation enzyme that catalyzes the covalent cotranslational attachment of fatty acids to the amino-terminal glycine residue of a number of proteins, leading to the modulation of various signaling molecules. In this study, we investigated the interaction of dengue viral proteins with host NMT and its subsequent effect on DENV. Our bioinformatics, molecular docking, and far-western blotting analyses demonstrated the interaction of viral envelope protein (E) with NMT. The gene expression of NMT was strongly elevated in a dependent manner during the viral replication phase in dendritic cells. Moreover, NMT gene silencing significantly inhibited DENV replication in dendritic cells. Further studies investigating the target cell types of other host factors are suggested.
AB - Dengue virus (DENV) causes dengue fever, a self-limiting disease that could be fatal due to serious complications. No specific treatment is currently available and the preventative vaccine is only partially protective. To develop a potential drug target for dengue fever, we need to understand its biology and pathogenesis thoroughly. N-myristoyltransferase (NMT) is an N-terminal protein lipidation enzyme that catalyzes the covalent cotranslational attachment of fatty acids to the amino-terminal glycine residue of a number of proteins, leading to the modulation of various signaling molecules. In this study, we investigated the interaction of dengue viral proteins with host NMT and its subsequent effect on DENV. Our bioinformatics, molecular docking, and far-western blotting analyses demonstrated the interaction of viral envelope protein (E) with NMT. The gene expression of NMT was strongly elevated in a dependent manner during the viral replication phase in dendritic cells. Moreover, NMT gene silencing significantly inhibited DENV replication in dendritic cells. Further studies investigating the target cell types of other host factors are suggested.
KW - N-myristoyltransferase1
KW - dengue virus
KW - envelope protein
KW - viral replication
UR - http://www.scopus.com/inward/record.url?scp=85062698294&partnerID=8YFLogxK
U2 - 10.1002/mbo3.831
DO - 10.1002/mbo3.831
M3 - Article
C2 - 30848105
AN - SCOPUS:85062698294
SN - 2045-8827
VL - 8
JO - MicrobiologyOpen
JF - MicrobiologyOpen
IS - 9
M1 - e00831
ER -