Structural and phenotypic analysis of Chikungunya virus RNA replication elements.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
26 09 2019
26 09 2019
Historique:
accepted:
16
07
2019
revised:
09
07
2019
received:
19
12
2018
pubmed:
28
7
2019
medline:
18
12
2019
entrez:
28
7
2019
Statut:
ppublish
Résumé
Chikungunya virus (CHIKV) is a re-emerging, pathogenic Alphavirus transmitted to humans by Aedes spp. mosquitoes. We have mapped the RNA structure of the 5' region of the CHIKV genome using selective 2'-hydroxyl acylation analysed by primer extension (SHAPE) to investigate intramolecular base-pairing at single-nucleotide resolution. Taking a structure-led reverse genetic approach, in both infectious virus and sub-genomic replicon systems, we identified six RNA replication elements essential to efficient CHIKV genome replication - including novel elements, either not previously analysed in other alphaviruses or specific to CHIKV. Importantly, through a reverse genetic approach we demonstrate that the replication elements function within the positive-strand genomic copy of the virus genome, in predominantly structure-dependent mechanisms during efficient replication of the CHIKV genome. Comparative analysis in human and mosquito-derived cell lines reveal that a novel element within the 5'UTR is essential for efficient replication in both host systems, while those in the adjacent nsP1 encoding region are specific to either vertebrate or invertebrate host cells. In addition to furthering our knowledge of fundamental aspects of the molecular virology of this important human pathogen, we foresee that results from this study will be important for rational design of a genetically stable attenuated vaccine.
Identifiants
pubmed: 31350895
pii: 5539885
doi: 10.1093/nar/gkz640
pmc: PMC6753490
doi:
Substances chimiques
RNA, Viral
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9296-9312Subventions
Organisme : Medical Research Council
ID : MR/N01054X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M011151/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/8
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Vector Borne Zoonotic Dis. 2006 Winter;6(4):325-37
pubmed: 17187566
Cell Mol Life Sci. 2012 Jan;69(1):103-13
pubmed: 21598019
PLoS One. 2009 Oct 22;4(10):e7468
pubmed: 19847293
PLoS Pathog. 2015 Apr 30;11(4):e1004863
pubmed: 25927359
J Virol. 2008 Sep;82(18):9008-22
pubmed: 18614633
Emerg Infect Dis. 2011 May;17(5):910-3
pubmed: 21529410
Nucleic Acids Res. 2003 Jul 1;31(13):3406-15
pubmed: 12824337
J Virol. 2009 Jan;83(2):993-1008
pubmed: 19004935
J Virol. 1990 Sep;64(9):4162-8
pubmed: 2384916
Mol Cell. 2001 Mar;7(3):581-91
pubmed: 11463383
Nucleic Acids Res. 2018 Apr 20;46(7):3657-3670
pubmed: 29361131
RNA. 2001 Nov;7(11):1638-51
pubmed: 11720292
Virology. 2009 Apr 25;387(1):211-21
pubmed: 19278709
BMC Bioinformatics. 2010 Mar 15;11:129
pubmed: 20230624
Virus Res. 2015 Aug 3;206:99-107
pubmed: 25630058
Lancet. 2007 Dec 1;370(9602):1840-6
pubmed: 18061059
MMWR Morb Mortal Wkly Rep. 2014 Jun 6;63(22):500-1
pubmed: 24898168
Nucleic Acids Res. 2015 Mar 11;43(5):2914-26
pubmed: 25712095
PLoS One. 2011;6(12):e28923
pubmed: 22205980
PLoS Pathog. 2007 Dec;3(12):e201
pubmed: 18069894
Nucleic Acids Res. 2012 Aug;40(14):6908-21
pubmed: 22561372
J Biol Chem. 2011 Jun 24;286(25):22521-34
pubmed: 21515677
RNA. 2010 Dec;16(12):2325-35
pubmed: 20980673
Genes Dev. 2006 Aug 15;20(16):2238-49
pubmed: 16882970
J Gen Virol. 2010 May;91(Pt 5):1218-23
pubmed: 20016034
Science. 2014 Feb 14;343(6172):783-7
pubmed: 24482115
J Virol. 1990 Apr;64(4):1639-47
pubmed: 2319648
Virology. 2008 Nov 10;381(1):123-35
pubmed: 18799181
Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):97-102
pubmed: 19109441
Virology. 2007 Jun 5;362(2):475-87
pubmed: 17292936
PLoS One. 2014 Aug 11;9(8):e104915
pubmed: 25111394
J Virol. 2004 May;78(10):4953-64
pubmed: 15113874
J Virol. 2009 Sep;83(17):8327-39
pubmed: 19515761
J Biol Chem. 2002 Dec 6;277(49):46923-31
pubmed: 12228229
J Virol. 2004 Jan;78(1):61-75
pubmed: 14671088
J Virol. 2015 Nov 18;90(3):1687-92
pubmed: 26581991
Bioinformatics. 2009 Aug 1;25(15):1974-5
pubmed: 19398448
EMBO J. 2001 Mar 15;20(6):1439-48
pubmed: 11250909
Int J Infect Dis. 2017 May;58:69-76
pubmed: 28288924
PLoS Negl Trop Dis. 2016 Jan 25;10(1):e0004402
pubmed: 26807575
RNA. 2013 Jan;19(1):63-73
pubmed: 23188808