Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein

Abstract Dengue virus (DENV) is an arthropod-borne Flavivirus that can cause a range of symptomatic disease in humans. There are four dengue viruses (DENV 1 to 4) and infection with one DENV only provides transient protection against a heterotypic virus. Second infections are often more severe as th...

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Autores principales:	Jeerang Wongtrakul, Thananya Thongtan, Supitcha Pannengpetch, Nitwara Wikan, Doungnapa Kantamala, Benjawan Kumrapich, Warissara Suwan, Duncan R. Smith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8c8b29a5a71e4dacb4dc12078a12c3b8
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spelling	oai:doaj.org-article:8c8b29a5a71e4dacb4dc12078a12c3b82021-12-02T19:04:25ZPhosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein10.1038/s41598-020-71407-x2045-2322https://doaj.org/article/8c8b29a5a71e4dacb4dc12078a12c3b82020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-71407-xhttps://doaj.org/toc/2045-2322Abstract Dengue virus (DENV) is an arthropod-borne Flavivirus that can cause a range of symptomatic disease in humans. There are four dengue viruses (DENV 1 to 4) and infection with one DENV only provides transient protection against a heterotypic virus. Second infections are often more severe as the disease is potentiated by antibodies from the first infection through a process known as antibody dependent enhancement (ADE) of infection. Phosphorylation is a major post-translational modification that can have marked effects on a number of processes. To date there has been little information on the phosphorylation changes induced by DENV infection. This study aimed to determine global phosphoproteome changes induced by DENV 2 in U937 cells infected under an ADE protocol. A 2-dimensional electrophoretic approach coupled with a phosphoprotein-specific dye and mass spectroscopic analysis identified 15 statistically significant differentially phosphorylated proteins upon DENV 2 infection. One protein identified as significantly differentially phosphorylated, pyruvate kinase M2 (PKM2) was validated. Treatment with a PKM2 inhibitor modestly reduced levels of infection and viral output, but no change was seen in cellular viral protein levels, suggesting that PKM2 acts on exocytic virus release. While the effect of inhibition of PKM2 was relatively modest, the results highlight the need for a greater understanding of the role of phosphoproteins in DENV infection.Jeerang WongtrakulThananya ThongtanSupitcha PannengpetchNitwara WikanDoungnapa KantamalaBenjawan KumrapichWarissara SuwanDuncan R. SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeerang Wongtrakul Thananya Thongtan Supitcha Pannengpetch Nitwara Wikan Doungnapa Kantamala Benjawan Kumrapich Warissara Suwan Duncan R. Smith Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein
description	Abstract Dengue virus (DENV) is an arthropod-borne Flavivirus that can cause a range of symptomatic disease in humans. There are four dengue viruses (DENV 1 to 4) and infection with one DENV only provides transient protection against a heterotypic virus. Second infections are often more severe as the disease is potentiated by antibodies from the first infection through a process known as antibody dependent enhancement (ADE) of infection. Phosphorylation is a major post-translational modification that can have marked effects on a number of processes. To date there has been little information on the phosphorylation changes induced by DENV infection. This study aimed to determine global phosphoproteome changes induced by DENV 2 in U937 cells infected under an ADE protocol. A 2-dimensional electrophoretic approach coupled with a phosphoprotein-specific dye and mass spectroscopic analysis identified 15 statistically significant differentially phosphorylated proteins upon DENV 2 infection. One protein identified as significantly differentially phosphorylated, pyruvate kinase M2 (PKM2) was validated. Treatment with a PKM2 inhibitor modestly reduced levels of infection and viral output, but no change was seen in cellular viral protein levels, suggesting that PKM2 acts on exocytic virus release. While the effect of inhibition of PKM2 was relatively modest, the results highlight the need for a greater understanding of the role of phosphoproteins in DENV infection.
format	article
author	Jeerang Wongtrakul Thananya Thongtan Supitcha Pannengpetch Nitwara Wikan Doungnapa Kantamala Benjawan Kumrapich Warissara Suwan Duncan R. Smith
author_facet	Jeerang Wongtrakul Thananya Thongtan Supitcha Pannengpetch Nitwara Wikan Doungnapa Kantamala Benjawan Kumrapich Warissara Suwan Duncan R. Smith
author_sort	Jeerang Wongtrakul
title	Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein
title_short	Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein
title_full	Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein
title_fullStr	Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein
title_full_unstemmed	Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein
title_sort	phosphoproteomic analysis of dengue virus infected u937 cells and identification of pyruvate kinase m2 as a differentially phosphorylated phosphoprotein
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/8c8b29a5a71e4dacb4dc12078a12c3b8
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Phosphoproteomic analysis of dengue virus infected U937 cells and identification of pyruvate kinase M2 as a differentially phosphorylated phosphoprotein

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