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Vector Competence Analyses on Aedes aegypti Mosquitoes using Zika Virus
Published on: May 31, 2020
The Aedes aegypti peritrophic matrix controls arbovirus vector competence through HPx1, a heme-induced peroxidase
Octavio A C Talyuli1, Jose Henrique M Oliveira2, Vanessa Bottino-Rojas1,3
1Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract:
Aedes aegypti mosquitoes are the main vectors of arboviruses. The peritrophic matrix (PM) is an extracellular layer that surrounds the blood bolus. It acts as an immune barrier that prevents direct contact of bacteria with midgut epithelial cells during blood digestion. Here, we describe a heme-dependent peroxidase, hereafter referred to as heme peroxidase 1 (HPx1). HPx1 promotes PM assembly and antioxidant ability, modulating vector competence. Mechanistically, the heme presence in a blood meal induces HPx1 transcriptional activation mediated by the E75 transcription factor. HPx1 knockdown increases midgut reactive oxygen species (ROS) production by the DUOX NADPH oxidase. Elevated ROS levels reduce microbiota growth while enhancing epithelial mitosis, a response to tissue damage. However, simultaneous HPx1 and DUOX silencing was not able to rescue bacterial population growth, as explained by increased expression of antimicrobial peptides (AMPs), which occurred only after double knockdown. This result revealed hierarchical activation of ROS and AMPs to control microbiota. HPx1 knockdown produced a 100-fold decrease in Zika and dengue 2 midgut infection, demonstrating the essential role of the mosquito PM in the modulation of arbovirus vector competence. Our data show that the PM connects blood digestion to midgut immunological sensing of the microbiota and viral infections.
Insights
A novel heme peroxidase 1 (HPx1) in Aedes aegypti mosquitoes is crucial for assembling the peritrophic matrix (PM). This protein modulates vector competence, significantly reducing Zika and dengue virus infections.
Area of Science:
- Vector biology
- Mosquito immunology
- Arbovirus transmission
Background:
- Aedes aegypti mosquitoes transmit arboviruses.
- The peritrophic matrix (PM) is an immune barrier in the mosquito midgut.
- Understanding mosquito midgut immunity is key to controlling arbovirus spread.
Purpose of the Study:
- To identify mosquito midgut proteins involved in immune barrier function.
- To investigate the role of heme peroxidase 1 (HPx1) in peritrophic matrix assembly and vector competence.
- To elucidate the mechanisms controlling midgut microbiota and arbovirus infection.
Main Methods:
- Described a novel heme-dependent peroxidase, HPx1.
- Utilized HPx1 knockdown and DUOX silencing in Aedes aegypti.
- Quantified reactive oxygen species (ROS) and antimicrobial peptide (AMP) expression.
- Assessed Zika and dengue virus infection levels in mosquito midguts.
Main Results:
- HPx1 promotes peritrophic matrix assembly and antioxidant ability.
- Heme in blood meals induces HPx1 transcription via the E75 transcription factor.
- HPx1 knockdown increases ROS production, reducing microbiota and enhancing epithelial mitosis.
- Hierarchical activation of ROS and AMPs controls microbiota.
- HPx1 knockdown significantly reduced Zika and dengue virus midgut infection.
Conclusions:
- The mosquito peritrophic matrix is essential for modulating arbovirus vector competence.
- HPx1 plays a critical role in midgut immunity and arbovirus transmission.
- The PM links blood digestion to the immune sensing of microbiota and viral infections.
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