Abstract
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.
Highlights
Dengue virus (DENV) infection is a neglected tropical disease that is widespread in tropical and subtropical regions
We per‐ formed in silico analysis to further test the DENV‐host interactions related to the replication cycle in dendritic cells, the primary senti‐ nel human target cell and the primary target for DENV replication and mediated immunity (Marovich et al, 2001; Schmid, Diamond, & Harris, 2014)
We included DENV Serotype 2 strain 16681 in the in silico analysis (Figure 2), which showed that DENV‐2 had a high abun‐ dance of predicted N‐myristoylation sites and that DENV‐2 strains
Summary
Dengue virus (DENV) infection is a neglected tropical disease that is widespread in tropical and subtropical regions. The fundamental role of NMT as being essential for cell survival makes it a potential drug target for the treatment of cancers, parasitic infections, and other infectious diseases. A study of the role of NMT in relation to human im‐ munodeficiency virus proteins has revealed that the myristoylation of Gag and Nef proteins is a key for viral replication and virulence (Seaton & Smith, 2008). Studies investigating Flavivirus NMT both in silico and in vitro are rare but are needed to develop therapeutic approaches based on the factors involved in viral‐host interactions. In this study, we performed both in silico and in vitro analysis to elucidate the role and effect of NMT under the conditions of Flavivirus infection. We used DENV as our study model, focusing on the biology and physio‐ logical relevance of host‐virus interactions
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