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Protocol for Dengue Infections in Mosquitoes A. aegypti and Infection Phenotype Determination
Published on: July 4, 2007
Low density lipopolyprotein inhibits flavivirus acquisition in Aedes aegypti
Z L Wagar1, M O Tree1, M C Mpoy1
1Foundational Sciences, Central Michigan University, College of Medicine, Mount Pleasant, MI, USA.
Abstract:
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.
Insights
Low-density lipoprotein (LDL) inhibits dengue and Zika virus acquisition in Aedes aegypti mosquitoes. This finding suggests
Area of Science:
- * Vector-borne disease research
- * Medical entomology
- * Virology
Background:
- * Aedes aegypti mosquitoes transmit critical human pathogens like dengue virus (DENV) and Zika virus (ZIKV).
- * Mosquitoes acquire these viruses from infected vertebrate bloodmeals, which contain factors influencing viral transmission.
- * Reduced low-density lipoprotein (LDL) levels correlate with severe DENV infections, suggesting a potential role for LDL in flavivirus acquisition.
Purpose of the Study:
- * To investigate the hypothesis that LDL is a modifiable factor influencing flavivirus acquisition in Aedes aegypti.
- * To determine the cellular mechanisms of LDL uptake in mosquito cells and midgut epithelium.
- * To evaluate the inhibitory effect of LDL on DENV and ZIKV infection in vitro and in vivo.
Main Methods:
- * Investigated LDL endocytosis in Ae. aegypti cells using dynamin-dependent assays.
- * Examined LDL accumulation in mosquito midgut epithelial cells during bloodmeal digestion.
- * Assessed the impact of LDL and high-density lipoprotein (HDL) pretreatment on DENV and ZIKV infection rates in vitro and in vivo.
Main Results:
- * LDL is endocytosed by Ae. aegypti cells in a dynamin-dependent manner.
- * LDL accumulates in the midgut epithelium during bloodmeal digestion.
- * LDL significantly inhibited DENV and ZIKV infection in vitro, and ZIKV infection in vivo, while HDL had no significant effect.
Conclusions:
- * Human LDL, commonly known as 'bad cholesterol,' acts as an inhibitor of flavivirus acquisition in Aedes aegypti.
- * This discovery highlights LDL as a modifiable factor with potential to disrupt vector-borne disease transmission.
- * Understanding these cellular interactions may lead to novel strategies for controlling diseases like dengue and Zika.
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