Low density lipopolyprotein inhibits flavivirus acquisition in Aedes aegypti

Low density lipopolyprotein inhibits flavivirus acquisition in Aedes aegypti

Aedes aegypti is the primary vector of a number of human pathogens including dengue virus (DENV) and Zika virus (ZIKV). Ae. aegypti acquires these viruses during the processing of bloodmeals obtained from an infected vertebrate host. Vertebrate blood contains a number of factors that have the potent...

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Bibliographic Details
Published in:Insect molecular biology Vol. 26; no. 6; pp. 734 - 742
Main Authors: Wagar, Z. L., Tree, M. O., Mpoy, M. C., Conway, M. J.
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01-12-2017
Subjects:
Aedes - metabolism
Aedes - virology
Aedes aegypti
Animals
Aquatic insects
Blood
Cholesterol
dengue
Dengue fever
Density
Disease transmission
Dynamin
Endocytosis
entry
Epithelial cells
Epithelial Cells - metabolism
Epithelium
Female
Flavivirus - physiology
High density lipoprotein
In vivo methods and tests
Infections
Intestinal Mucosa - metabolism
Lipoproteins, LDL - metabolism
Low density lipoprotein
Midgut
Mosquitoes
Pathogens
Pretreatment
Vector-borne diseases
Viral diseases
Viruses
entry
cholesterol
aedes aegypti
blood
dengue
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Summary:Aedes aegypti is the primary vector of a number of human pathogens including dengue virus (DENV) and Zika virus (ZIKV). Ae. aegypti acquires these viruses during the processing of bloodmeals obtained from an infected vertebrate host. Vertebrate blood contains a number of factors that have the potential to modify virus acquisition in the mosquito. Interestingly, low density lipopolyprotein (LDL) levels are decreased during severe DENV infection. Accordingly, we hypothesized that LDL is a modifiable factor that can influence flavivirus acquisition in the mosquito. We found that LDL is endocytosed by Ae. aegypti cells in a dynamin‐dependent manner. LDL is also endocytosed by midgut epithelial cells and accumulates at the luminal midgut epithelium during bloodmeal digestion. Importantly, pretreatment with LDL, but not high density lipopolyprotein (HDL), significantly inhibited both DENV and ZIKV infection in vitro, and LDL inhibited ZIKV infection in vivo. This study identifies human LDL or ‘bad cholesterol’ as a modifiable factor that can inhibit flavivirus acquisition in Ae. aegypti. Identification of modifiable blood factors and critical cellular interactions that mediate pathogen acquisition may lead to novel strategies to disrupt the transmission cycle of vector‐borne diseases.
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ISSN:0962-1075
1365-2583
DOI:10.1111/imb.12334