The interaction between Dengue virus (DENV) and the Aedes mosquito involves specific mosquito proteins that can either enhance or inhibit viral infection and transmission.
Mosquito Salivary Gland Proteins.
Several proteins in Aedes aegypti saliva modulate DENV infection, and changes in their expression levels can affect transmission efficiency:
- AaSG34 (34 kDa salivary protein): Promotes DENV replication in the mosquito’s salivary glands and enhances virus transmission to a mammalian host by suppressing the host’s innate immune responses.
- D7 Proteins (long and short forms): These proteins assist in blood feeding by scavenging biogenic amines. They can inhibit DENV infection in vitro, but antibodies against them in humans may enhance disease severity, potentially by preventing the protein’s normal function.
- Aegyptin: An inhibitor of blood clot formation whose abundance decreases in the saliva of DENV-infected mosquitoes. When co-inoculated with DENV, aegyptin helps modulate the infection by increasing the vertebrate host’s immune response, which ultimately reduces viral titer.
- AaVA-1 (Aegypti venom allergen 1): Enhances DENV replication in dendritic cells and macrophages by promoting autophagy.
Mosquito Midgut and Other Cell Proteins
DENV must infect and pass through the mosquito’s midgut to establish a systemic infection. This process involves specific receptors and host factors:
- EPrRec (Envelope Protein Receptor, ~31 kDa): Identified as AAEL011180, this protein in the Aedes aegypti midgut is a key receptor for the DENV envelope (E) protein. Impairing its expression significantly reduces the prevalence of DENV midgut infection.
- Enolase (~57/67 kDa): A glycolytic enzyme found in the mosquito midgut brush border that binds to DENV, suggesting it may function as a viral receptor.
- Other Binding Proteins: Additional mosquito proteins that bind to DENV include beta-adrenergic receptor kinase (beta-ARK), translation elongation factor EF-1 alpha/Tu, and cadherin.
- Pupal Cuticle Protein (AaPC): This protein inhibits DENV infection by directly binding to the virus and causing aggregation, which blocks the virus-cell fusion stage.
- Heat Shock Protein 70 (HSP70) and Elongation Factor 1 Alpha (EF1A): Both of these proteins have been shown to be involved in the DENV viral life cycle, with inhibition blocking viral replication. (Kris Cahyo Mulyatno)
