Potential Phosphorylation of Viral Nonstructural Protein 1 in Dengue Virus Infection.
LC-MS/MS
NS1
dengue virus
phosphorylation
virus production
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
17 07 2021
17 07 2021
Historique:
received:
09
06
2021
revised:
12
07
2021
accepted:
14
07
2021
entrez:
10
8
2021
pubmed:
11
8
2021
medline:
19
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34372598
pii: v13071393
doi: 10.3390/v13071393
pmc: PMC8310366
pii:
doi:
Substances chimiques
NS1 protein, Dengue virus type 2
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
PLoS Pathog. 2007 Nov;3(11):e183
pubmed: 18052531
Virus Res. 2005 Sep;112(1-2):85-94
pubmed: 15878791
Nature. 2013 Apr 25;496(7446):504-7
pubmed: 23563266
Cell Host Microbe. 2009 Apr 23;5(4):365-75
pubmed: 19380115
Proc Natl Acad Sci U S A. 2011 May 10;108(19):8003-8
pubmed: 21518917
Bioessays. 2015 May;37(5):489-94
pubmed: 25761098
Virol J. 2015 Feb 06;12:14
pubmed: 25890165
Biochem Biophys Res Commun. 2007 Nov 3;362(4):1051-6
pubmed: 17825259
J Immunol. 2016 Nov 15;197(10):4053-4065
pubmed: 27798151
J Virol. 2015 Dec;89(23):11871-83
pubmed: 26378175
FASEB J. 2000 Aug;14(11):1603-10
pubmed: 10928995
J Biol Chem. 2011 Apr 1;286(13):11506-18
pubmed: 21177246
J Gen Virol. 2008 Oct;89(Pt 10):2492-2500
pubmed: 18796718
Clin Exp Immunol. 1979 Apr;36(1):46-53
pubmed: 380857
J Exp Med. 2010 Apr 12;207(4):793-806
pubmed: 20308361
J Infect Dis. 2020 Dec 15;:
pubmed: 33319249
Electrophoresis. 1999 Dec;20(18):3551-67
pubmed: 10612281
J Virol. 1997 Dec;71(12):9608-17
pubmed: 9371625
Trends Pharmacol Sci. 2008 Aug;29(8):413-20
pubmed: 18606460
Virology. 1996 Jun 1;220(1):232-40
pubmed: 8659120
Sci Transl Med. 2015 Sep 9;7(304):304ra141
pubmed: 26355030
Science. 2014 Feb 21;343(6173):881-5
pubmed: 24505133
Virol J. 2013 Nov 18;10:339
pubmed: 24245822
Virus Res. 1997 May;49(1):9-15
pubmed: 9178492
BMC Infect Dis. 2019 Aug 28;19(1):750
pubmed: 31455279
J Virol. 1998 Jul;72(7):6199-206
pubmed: 9621090
J Infect Dis. 2006 Apr 15;193(8):1078-88
pubmed: 16544248
J Virol. 2009 Sep;83(18):9195-205
pubmed: 19587048
Curr Opin Microbiol. 2008 Aug;11(4):369-77
pubmed: 18644250
Virology. 2010 Jan 5;396(1):30-6
pubmed: 19897220
Viruses. 2015 Oct 12;7(10):5257-73
pubmed: 26473910
J Cell Biol. 2007 Apr 9;177(1):127-37
pubmed: 17403928
J Immunol. 2011 Jul 1;187(1):424-33
pubmed: 21642539
J Cell Physiol. 2015 Feb;230(2):449-63
pubmed: 25078272
PLoS One. 2018 Mar 16;13(3):e0194399
pubmed: 29547653
J Virol. 2005 Sep;79(17):11403-11
pubmed: 16103191
Biochim Biophys Acta. 2016 Sep;1864(9):1270-1280
pubmed: 27108190
Front Immunol. 2020 Jun 18;11:1252
pubmed: 32655561
J Virol Methods. 2007 Jun;142(1-2):67-80
pubmed: 17331594
J Virol. 2011 Feb;85(3):1158-73
pubmed: 21084474
J Biol Chem. 1995 Aug 11;270(32):19100-6
pubmed: 7642575
PLoS Pathog. 2015 Nov 12;11(11):e1005277
pubmed: 26562291
Cell Rep. 2018 Jan 30;22(5):1364
pubmed: 29386121
J Gen Virol. 2018 Oct;99(10):1391-1406
pubmed: 30102148
Trends Biochem Sci. 2000 Dec;25(12):596-601
pubmed: 11116185
Arch Virol. 2011 Jul;156(7):1275-9
pubmed: 21424730
J Immunol. 1970 Dec;105(6):1565-8
pubmed: 5483833
Virology. 2015 Oct;484:113-126
pubmed: 26092250
J Gen Virol. 2020 May;101(5):484-496
pubmed: 32141809
Thromb Haemost. 2008 May;99(5):936-43
pubmed: 18449425
PLoS One. 2013;8(3):e57514
pubmed: 23516407
J Virol. 2013 Dec;87(23):12667-74
pubmed: 24049164
Virology. 2011 May 10;413(2):253-64
pubmed: 21429549
N Engl J Med. 2018 Jul 26;379(4):327-340
pubmed: 29897841
Nat Rev Mol Cell Biol. 2007 Jul;8(7):530-41
pubmed: 17585314
J Infect Dis. 2002 Oct 15;186(8):1165-8
pubmed: 12355369
PLoS Negl Trop Dis. 2020 Nov 20;14(11):e0008835
pubmed: 33216752
Curr Opin Virol. 2020 Aug;43:71-78
pubmed: 33086187
Virology. 1989 Jul;171(1):302-5
pubmed: 2525840
Front Genet. 2014 Aug 07;5:270
pubmed: 25147561
J Clin Microbiol. 2000 Mar;38(3):1053-7
pubmed: 10698995
PLoS Pathog. 2019 May 9;15(5):e1007736
pubmed: 31071189
Rev Med Virol. 2012 May;22(3):166-81
pubmed: 22113983
Sci Transl Med. 2015 Sep 9;7(304):304ra142
pubmed: 26355031
Virology. 1988 Jan;162(1):187-96
pubmed: 2827377
Virology. 2016 Sep;496:227-236
pubmed: 27348054
J Infect Dis. 2009 Oct 15;200(8):1261-70
pubmed: 19754307
J Virol. 2009 Jun;83(11):5408-18
pubmed: 19279106
Am J Trop Med Hyg. 1985 Jan;34(1):162-9
pubmed: 2578750
Am J Trop Med Hyg. 1982 Jul;31(4):830-6
pubmed: 6285749
J Gen Virol. 2012 Apr;93(Pt 4):771-779
pubmed: 22238236
Mol Cell Proteomics. 2011 Dec;10(12):M111.012187
pubmed: 21911577
PeerJ. 2020 Sep 25;8:e9988
pubmed: 33033661
J Virol. 1997 Sep;71(9):6650-61
pubmed: 9261387
J Clin Microbiol. 2002 Feb;40(2):376-81
pubmed: 11825945
Viruses. 2017 Apr 24;9(4):
pubmed: 28441781
J Virol. 1999 Jul;73(7):6104-10
pubmed: 10364366
J Virol Methods. 2003 Apr;109(1):55-61
pubmed: 12668268
PLoS Pathog. 2015 Jul 30;11(7):e1005053
pubmed: 26226614