Protein Disulfide Isomerase Mediates Dengue Virus Entry in Association with Lipid Rafts

2015 ◽  
Vol 28 (3) ◽  
pp. 153-160 ◽  
Author(s):  
Drishya Diwaker ◽  
Kamla P. Mishra ◽  
Lilly Ganju ◽  
Shashi B. Singh
Keyword(s):  
Dengue Virus ◽  
Lipid Rafts ◽  
Protein Disulfide Isomerase ◽  
Virus Entry ◽  
Disulfide Isomerase ◽  
Protein Disulfide

scholarly journals Protein Disulfide Isomerase Inhibitor Suppresses Viral Replication and Production during Antibody-Dependent Enhancement of Dengue Virus Infection in Human Monocytic Cells

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 155 ◽  
Author(s):  
Nantapon Rawarak ◽  
Aroonroong Suttitheptumrong ◽  
Onrapak Reamtong ◽  
Kobporn Boonnak ◽  
Sa-nga Pattanakitsakul
Keyword(s):  
Dengue Virus ◽  
Protein Disulfide Isomerase ◽  
Early Stage ◽  
Secondary Infection ◽  
Protein Translation ◽  
Virus Infectivity ◽  
Disulfide Isomerase ◽  
Antibody Dependent Enhancement ◽  
Altered Proteins ◽  
Protein Disulfide

One of several mechanisms that leads to the development of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) is called antibody-dependent enhancement (ADE). Monocytes can be infected by the ADE phenomenon, which occurs in dengue secondary infection. This study aimed to investigate the proteins involved in ADE of DENV infection in the human monocytic cell line U937. The phosphoproteins were used to perform and analyze for protein expression using mass spectrometry (GeLC-MS/MS). The differential phosphoproteins revealed 1131 altered proteins compared between isotype- and DENV-specific antibody-treated monocytes. The altered proteins revealed 558 upregulated proteins and 573 downregulated proteins. Protein disulfide isomerase (PDI), which is an enzyme that had a high-ranking fold change and that catalyzes the formation, breakage, and rearrangement of disulfide bonds within a protein molecule, was selected for further study. PDI was found to be important for dengue virus infectivity during the ADE model. The effect of PDI inhibition was also shown to be involved in the early stage of life cycle by time-of-drug-addition assay. These results suggest that PDI is important for protein translation and virion assembly of dengue virus during infection in human monocytes, and it may play a significant role as a chaperone to stabilize dengue protein synthesis.

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