Expression of fatty acid synthase genes and their role in development and arboviral infection of Aedes aegypti.
AaegL5 genome assembly
Aag2 cells
Aedes aegypti
Dengue virus
FAS
Fatty acid synthase
Lipid
Lipid metabolism
Journal
Parasites & vectors
ISSN: 1756-3305
Titre abrégé: Parasit Vectors
Pays: England
ID NLM: 101462774
Informations de publication
Date de publication:
27 Jun 2022
27 Jun 2022
Historique:
received:
08
02
2022
accepted:
24
05
2022
entrez:
27
6
2022
pubmed:
28
6
2022
medline:
30
6
2022
Statut:
epublish
Résumé
Fatty acids are the building blocks of complex lipids essential for living organisms. In mosquitoes, fatty acids are involved in cell membrane production, energy conservation and expenditure, innate immunity, development and reproduction. Fatty acids are synthesized by a multifunctional enzyme complex called fatty acid synthase (FAS). Several paralogues of FAS were found in the Aedes aegypti mosquito. However, the molecular characteristics and expression of some of these paralogues have not been investigated. Genome assemblies of Ae. aegypti were analyzed, and orthologues of human FAS was identified. Phylogenetic analysis and in silico molecular characterization were performed to identify the functional domains of the Ae. aegypti FAS (AaFAS). Quantitative analysis and loss-of-function experiments were performed to determine the significance of different AaFAS transcripts in various stages of development, expression following different diets and the impact of AaFAS on dengue virus, serotype 2 (DENV2) infection and transmission. We identified seven putative FAS genes in the Ae. aegypti genome assembly, based on nucleotide similarity to the FAS proteins (tBLASTn) of humans, other mosquitoes and invertebrates. Bioinformatics and molecular analyses suggested that only five of the AaFAS genes produce mRNA and therefore represent complete gene models. Expression levels of AaFAS varied among developmental stages and between male and female Ae. aegypti. Quantitative analyses revealed that expression of AaFAS1, the putative orthologue of the human FAS, was highest in adult females. Transient knockdown (KD) of AaFAS1 did not induce a complete compensation by other AaFAS genes but limited DENV2 infection of Aag2 cells in culture and the midgut of the mosquito. AaFAS1 is the predominant AaFAS in adult mosquitoes. It has the highest amino acid similarity to human FAS and contains all enzymatic domains typical of human FAS. AaFAS1 also facilitated DENV2 replication in both cell culture and in mosquito midguts. Our data suggest that AaFAS1 may play a role in transmission of dengue viruses and could represent a target for intervention strategies.
Sections du résumé
BACKGROUND
BACKGROUND
Fatty acids are the building blocks of complex lipids essential for living organisms. In mosquitoes, fatty acids are involved in cell membrane production, energy conservation and expenditure, innate immunity, development and reproduction. Fatty acids are synthesized by a multifunctional enzyme complex called fatty acid synthase (FAS). Several paralogues of FAS were found in the Aedes aegypti mosquito. However, the molecular characteristics and expression of some of these paralogues have not been investigated.
METHODS
METHODS
Genome assemblies of Ae. aegypti were analyzed, and orthologues of human FAS was identified. Phylogenetic analysis and in silico molecular characterization were performed to identify the functional domains of the Ae. aegypti FAS (AaFAS). Quantitative analysis and loss-of-function experiments were performed to determine the significance of different AaFAS transcripts in various stages of development, expression following different diets and the impact of AaFAS on dengue virus, serotype 2 (DENV2) infection and transmission.
RESULTS
RESULTS
We identified seven putative FAS genes in the Ae. aegypti genome assembly, based on nucleotide similarity to the FAS proteins (tBLASTn) of humans, other mosquitoes and invertebrates. Bioinformatics and molecular analyses suggested that only five of the AaFAS genes produce mRNA and therefore represent complete gene models. Expression levels of AaFAS varied among developmental stages and between male and female Ae. aegypti. Quantitative analyses revealed that expression of AaFAS1, the putative orthologue of the human FAS, was highest in adult females. Transient knockdown (KD) of AaFAS1 did not induce a complete compensation by other AaFAS genes but limited DENV2 infection of Aag2 cells in culture and the midgut of the mosquito.
CONCLUSION
CONCLUSIONS
AaFAS1 is the predominant AaFAS in adult mosquitoes. It has the highest amino acid similarity to human FAS and contains all enzymatic domains typical of human FAS. AaFAS1 also facilitated DENV2 replication in both cell culture and in mosquito midguts. Our data suggest that AaFAS1 may play a role in transmission of dengue viruses and could represent a target for intervention strategies.
Identifiants
pubmed: 35761349
doi: 10.1186/s13071-022-05336-1
pii: 10.1186/s13071-022-05336-1
pmc: PMC9235097
doi:
Substances chimiques
Fatty Acids
0
Insect Proteins
0
Fatty Acid Synthases
EC 2.3.1.85
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
233Subventions
Organisme : NIAID NIH HHS
ID : R01 AI151166
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : R01AI151166
Informations de copyright
© 2022. The Author(s).
Références
Nucleic Acids Res. 1988 Nov 25;16(22):10881-90
pubmed: 2849754
Bioinformatics. 2007 Nov 1;23(21):2947-8
pubmed: 17846036
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17345-50
pubmed: 20855599
BMC Bioinformatics. 2007 Aug 09;8:298
pubmed: 17688688
Virology. 2015 May;479-480:418-33
pubmed: 25746936
J Med Entomol. 2003 Mar;40(2):150-8
pubmed: 12693842
Bioinformatics. 1998;14(4):380-1
pubmed: 9632837
BMC Bioinformatics. 2009 Dec 15;10:421
pubmed: 20003500
Insect Biochem Mol Biol. 2011 Dec;41(12):946-55
pubmed: 21971482
Science. 2007 Jun 22;316(5832):1718-23
pubmed: 17510324
Mol Biol Evol. 2015 Feb;32(2):456-71
pubmed: 25425561
Annu Rev Biochem. 2005;74:791-831
pubmed: 15952903
Mol Syst Biol. 2011 Oct 11;7:539
pubmed: 21988835
Nucleic Acids Res. 2015 Jan;43(Database issue):D707-13
pubmed: 25510499
J Nutr. 1980 Jun;110(6):1152-60
pubmed: 7381586
J Exp Biol. 2002 Dec;205(Pt 23):3623-30
pubmed: 12409488
PLoS Pathog. 2012;8(3):e1002584
pubmed: 22457619
Gastroenterology. 2009 Dec;137(6):2170-2
pubmed: 19878748
PLoS Pathog. 2018 Feb 15;14(2):e1006853
pubmed: 29447265
Am J Trop Med Hyg. 2002 Jul;67(1):85-92
pubmed: 12363070
J Virol. 2014 Jun;88(12):6793-804
pubmed: 24696471
Insect Biochem Mol Biol. 2004 Sep;34(9):919-25
pubmed: 15350611
Virology. 1986 Dec;155(2):365-77
pubmed: 3024394
PLoS One. 2011;6(9):e24970
pubmed: 21949814
PLoS Negl Trop Dis. 2015 Jun 26;9(6):e0003894
pubmed: 26115104
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
Science. 2008 Sep 5;321(5894):1315-22
pubmed: 18772430
PLoS Pathog. 2009 Feb;5(2):e1000299
pubmed: 19214215
J Insect Physiol. 1979;25(6):495-502
pubmed: 489998
BMC Genomics. 2015 Nov 14;16:941
pubmed: 26573520
Methods. 2005 Jun;36(2):207-24
pubmed: 15894491
Annu Rev Entomol. 2010;55:207-25
pubmed: 19725772
J Insect Physiol. 2001 Jun;47(6):623-627
pubmed: 11249951
Virol J. 2017 Feb 13;14(1):28
pubmed: 28193229
Insect Mol Biol. 2010 Dec;19(6):753-63
pubmed: 20738425
J Virol. 2014 May;88(9):4687-97
pubmed: 24522909
Science. 2006 Mar 3;311(5765):1283-7
pubmed: 16513982
Genome Biol. 2013 Aug 30;14(8):R93
pubmed: 24000942
Insect Sci. 2013 Oct;20(5):585-600
pubmed: 23956110
BMC Genomics. 2016 Jan 06;17:32
pubmed: 26738925
J Insect Physiol. 2004 Apr;50(4):337-49
pubmed: 15081827
Evolution. 2017 Dec;71(12):2871-2884
pubmed: 28875541
Lipids. 1975 Nov;10(11):686-94
pubmed: 1196018