Publication: Potential phosphorylation of viral nonstructural protein 1 in dengue virus infection
Issued Date
2021-07-01
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ISSN
19994915
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2-s2.0-85111427823
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Mahidol University
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SCOPUS
Bibliographic Citation
Viruses. Vol.13, No.7 (2021)
Suggested Citation
Thanyaporn Dechtawewat, Sittiruk Roytrakul, Yodying Yingchutrakul, Sawanya Charoenlappanit, Bunpote Siridechadilok, Thawornchai Limjindaporn, Arunothai Mangkang, Tanapan Prommool, Chunya Puttikhunt, Pucharee Songprakhon, Kessiri Kongmanas, Nuttapong Kaewjew, Panisadee Avirutnan, Pa Thai Yenchitsomanus, Prida Malasit, Sansanee Noisakran Potential phosphorylation of viral nonstructural protein 1 in dengue virus infection. Viruses. Vol.13, No.7 (2021). doi:10.3390/v13071393 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/77261
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Title
Potential phosphorylation of viral nonstructural protein 1 in dengue virus infection
Author(s)
Thanyaporn Dechtawewat
Sittiruk Roytrakul
Yodying Yingchutrakul
Sawanya Charoenlappanit
Bunpote Siridechadilok
Thawornchai Limjindaporn
Arunothai Mangkang
Tanapan Prommool
Chunya Puttikhunt
Pucharee Songprakhon
Kessiri Kongmanas
Nuttapong Kaewjew
Panisadee Avirutnan
Pa Thai Yenchitsomanus
Prida Malasit
Sansanee Noisakran
Sittiruk Roytrakul
Yodying Yingchutrakul
Sawanya Charoenlappanit
Bunpote Siridechadilok
Thawornchai Limjindaporn
Arunothai Mangkang
Tanapan Prommool
Chunya Puttikhunt
Pucharee Songprakhon
Kessiri Kongmanas
Nuttapong Kaewjew
Panisadee Avirutnan
Pa Thai Yenchitsomanus
Prida Malasit
Sansanee Noisakran
Other Contributor(s)
Abstract
Dengue virus (DENV) infection causes a spectrum of dengue diseases that have unclear underlying mechanisms. Nonstructural protein 1 (NS1) is a multifunctional protein of DENV that is involved in DENV infection and dengue pathogenesis. This study investigated the potential post-translational modification of DENV NS1 by phosphorylation following DENV infection. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), 24 potential phosphorylation sites were identified in both cell-associated and extracellular NS1 proteins from three different cell lines infected with DENV. Cell-free kinase assays also demonstrated kinase activity in purified preparations of DENV NS1 proteins. Further studies were conducted to determine the roles of specific phosphorylation sites on NS1 proteins by site-directed mutagenesis with alanine substitution. The T27A and Y32A mutations had a deleterious effect on DENV infectivity. The T29A, T230A, and S233A mutations significantly decreased the production of infectious DENV but did not affect relative levels of intracellular DENV NS1 expression or NS1 secretion. Only the T230A mutation led to a significant reduction of detectable DENV NS1 dimers in virus-infected cells; however, none of the mutations interfered with DENV NS1 oligomeric formation. These findings highlight the importance of DENV NS1 phosphorylation that may pave the way for future target-specific antiviral drug design.