Multiple Salivary Proteins from Aedes aegypti Mosquito Bind to the Zika Virus Envelope Protein

Abstract

Aedes aegypti mosquitoes are important vectors of several debilitating and deadly arthropod-borne (arbo) viruses, including Yellow Fever virus, Dengue virus, West Nile virus and Zika virus (ZIKV). Arbovirus transmission occurs when an infected mosquito probes the host’s skin in search of a blood meal. Salivary proteins from mosquitoes help to acquire blood and have also been shown to enhance pathogen transmission in vivo and in vitro. Here, we evaluated the interaction of mosquito salivary proteins with ZIKV by surface plasmon resonance and enzyme-linked immunosorbent assay. We found that three salivary proteins AAEL000793, AAEL007420, and AAEL006347 bind to the envelope protein of ZIKV with nanomolar affinities. Similar results were obtained using virus-like particles in binding assays. These interactions have no effect on viral replication in cultured endothelial cells and keratinocytes. Additionally, we found detectable antibody levels in ZIKV and DENV serum samples against the recombinant proteins that interact with ZIKV. These results highlight complex interactions between viruses, salivary proteins and antibodies that could be present during viral transmissions.

A deeper insight into the sialome of male and female Ochlerotatus triseriatus mosquitoes

“…Together, these studies suggest the potential role of antigen 5-like proteins in blood acquisition. In a recent study, Valenzuela-Leon et al (2022) found that a member of this family bound to the Zika virus envelope protein with nanomolar affinities. However, this interaction had no effect on viral replication in cultured endothelial cells and keratinocytes.…”

Identification of Aedes aegypti salivary gland proteins interacting with human immune receptor proteins

“…ADA2 also removes adenosine from bite site and aids in a prolonged blood-feeding [ 45 ] and has been shown to partially enhance dengue and Zika virus infection in human THP-1 cells [ 3 ]. Recently, apyrase was shown to directly interact with ZIKV [ 46 ]. The above analysis suggests the importance of 1) the interactions of vector SGPs such as ADA2, D7 proteins (AAEL006424 and AAEL006417 ), apyrase, and aegyptin, with host receptors and 2) the interaction of some SGPs with the pathogen/host molecules.…”

“…AaVA-1 is a crucial target that promotes DENV and ZIKV infection in vitro in human THP-1 cells and in vivo in mouse models via interaction with human leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) [ 3 ]. Recently, AaVA-1 was shown to directly interact with ZIKV [ 46 ]. This suggests the potential role of AaVA-1-CD4 and AaVA-1-DC-SIGN interactions on viral infection in human hosts.…”

Antibodies to Aedes aegypti D7L salivary proteins as a new serological tool to estimate human exposure to Aedes mosquitoes

“…The human cell line HEK293 was used to recombinantly express 18 Ae. aegypti recombinant proteins, as described previously ( 20 ). After identification of the most immunogenic proteins, the production of AeApyrase, AeD7L1, AeD7L2, NIH-23, and NIH-27 was scaled up, and they were codon-optimized for mammalian expression, synthesized with a carboxyl-terminal HIS-tag (GenScript, Piscataway, NJ, USA), and cloned into pHEK293 Ultra Expression Vectors (Takara, Mountain View, CA, USA).…”