PMID- 35761349
OWN - NLM
STAT- MEDLINE
DCOM- 20220629
LR  - 20230108
IS  - 1756-3305 (Electronic)
IS  - 1756-3305 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Jun 27
TI  - Expression of fatty acid synthase genes and their role in development and 
      arboviral infection of Aedes aegypti.
PG  - 233
LID - 10.1186/s13071-022-05336-1 [doi]
LID - 233
AB  - 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: 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: 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: 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.
CI  - (c) 2022. The Author(s).
FAU - Chotiwan, Nunya
AU  - Chotiwan N
AD  - Department of Microbiology, Immunology and Pathology, Colorado State University, 
      Fort Collins, CO, USA.
AD  - Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, 
      Mahidol University, Samut Prakan, Thailand.
FAU - Brito-Sierra, Carlos A
AU  - Brito-Sierra CA
AD  - Department of Entomology, Purdue University, West Lafayette, IL, USA.
AD  - Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue 
      University, West Lafayette, IN, USA.
AD  - Lilly Research Laboratories, Eli Lilly and Company, IN, Indianapolis, USA.
FAU - Ramirez, Gabriella
AU  - Ramirez G
AD  - Department of Microbiology, Immunology and Pathology, Colorado State University, 
      Fort Collins, CO, USA.
FAU - Lian, Elena
AU  - Lian E
AD  - Department of Microbiology, Immunology and Pathology, Colorado State University, 
      Fort Collins, CO, USA.
FAU - Grabowski, Jeffrey M
AU  - Grabowski JM
AD  - Department of Entomology, Purdue University, West Lafayette, IL, USA.
AD  - Foundation for Advanced Education in the Sciences at the NIH, Bethesda, MD, USA.
FAU - Graham, Babara
AU  - Graham B
AD  - Department of Microbiology, Immunology and Pathology, Colorado State University, 
      Fort Collins, CO, USA.
FAU - Hill, Catherine A
AU  - Hill CA
AD  - Department of Entomology, Purdue University, West Lafayette, IL, USA.
AD  - Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue 
      University, West Lafayette, IN, USA.
FAU - Perera, Rushika
AU  - Perera R
AUID- ORCID: 0000-0001-6798-2537
AD  - Department of Microbiology, Immunology and Pathology, Colorado State University, 
      Fort Collins, CO, USA. rushika.perera@colostate.edu.
LA  - eng
GR  - R01 AI151166/AI/NIAID NIH HHS/United States
GR  - R01AI151166/National Institute of Allergy and Infectious Diseases/
PT  - Journal Article
DEP - 20220627
PL  - England
TA  - Parasit Vectors
JT  - Parasites & vectors
JID - 101462774
RN  - 0 (Fatty Acids)
RN  - 0 (Insect Proteins)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
SB  - IM
MH  - *Aedes/genetics/virology
MH  - Animals
MH  - *Arbovirus Infections
MH  - *Dengue
MH  - Dengue Virus
MH  - *Fatty Acid Synthases/genetics
MH  - Fatty Acids
MH  - Female
MH  - Humans
MH  - Insect Proteins/genetics
MH  - Male
MH  - Mosquito Vectors/virology
MH  - Phylogeny
MH  - Virus Replication
PMC - PMC9235097
OTO - NOTNLM
OT  - AaegL5 genome assembly
OT  - Aag2 cells
OT  - Aedes aegypti
OT  - Dengue virus
OT  - FAS
OT  - Fatty acid synthase
OT  - Lipid
OT  - Lipid metabolism
COIS- The authors have no competing interests.
EDAT- 2022/06/28 06:00
MHDA- 2022/06/30 06:00
PMCR- 2022/06/27
CRDT- 2022/06/27 23:47
PHST- 2022/02/08 00:00 [received]
PHST- 2022/05/24 00:00 [accepted]
PHST- 2022/06/27 23:47 [entrez]
PHST- 2022/06/28 06:00 [pubmed]
PHST- 2022/06/30 06:00 [medline]
PHST- 2022/06/27 00:00 [pmc-release]
AID - 10.1186/s13071-022-05336-1 [pii]
AID - 5336 [pii]
AID - 10.1186/s13071-022-05336-1 [doi]
PST - epublish
SO  - Parasit Vectors. 2022 Jun 27;15(1):233. doi: 10.1186/s13071-022-05336-1.