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

Introduction: are the most prolific mosquito vectors in the world. Found on every continent, they can effectively transmit various arboviruses, including the dengue virus which continues to cause outbreaks worldwide and is spreading into previously non-endemic areas. The lack of widely available dengue vaccines accentuates the importance of targeted vector control strategies to reduce the dengue burden.

Structural and functional comparisons of salivary α-glucosidases from the mosquito vectors Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus.

Mosquito vectors of medical importance both blood and sugar feed, and their saliva contains bioactive molecules that aid in both processes. Although it has been shown that the salivary glands of several mosquito species exhibit α-glucosidase activities, the specific enzymes responsible for sugar digestion remain understudied. We therefore expressed and purified three recombinant salivary α-glucosidases from the mosquito vectors Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus and compared their functions and structures.

Skin muscle is the initial site of viral replication for arboviral bunyavirus infection.

The first step in disease pathogenesis for arboviruses is the establishment of infection following vector transmission. For La Crosse virus (LACV), the leading cause of pediatric arboviral encephalitis in North America, and other orthobunyaviruses, the initial course of infection in the skin is not well understood. Using an intradermal (ID) model of LACV infection in mice, we find that the virus infects and replicates nearly exclusively within skin-associated muscle cells of the panniculus carnosus (PC) and not in epidermal or dermal cells like most other arbovirus families.

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

Introduction: are the most prolific mosquito vectors in the world. Found on every continent, they can effectively transmit various arboviruses, including the dengue virus which continues to cause outbreaks worldwide and is spreading into previously non-endemic areas. The lack of widely available dengue vaccines accentuates the importance of targeted vector control strategies to reduce the dengue burden.

Complement receptor 1 is the human erythrocyte receptor for erythrocyte binding protein.

The discovery that Africans were resistant to infection by () led to the conclusion that invasion relied on the Duffy Binding Protein (PvDBP) interacting with the Duffy Antigen Receptor for Chemokines (DARC) expressed on erythrocytes. However, the recent reporting of infections in DARC-negative Africans suggests that the parasite might use an alternate invasion pathway to infect DARC-negative reticulocytes. To identify the parasite ligands and erythrocyte receptors that enable invasion of both DARC-positive and -negative erythrocytes, we expressed region II containing the Duffy Binding-Like (DBL) domain of erythrocyte binding protein (PvEBP-RII) and verified that the DBL domain binds to both DARC-positive and -negative erythrocytes.

saliva modulates inflammasome activation and facilitates flavivirus infection .

Mosquito borne flaviviruses such as dengue and Zika represent a major public health problem due to globalization and propagation of susceptible vectors worldwide. Vertebrate host responses to dengue and Zika infections include the processing and release of pro-inflammatory cytokines through the activation of inflammasomes, resulting in disease severity and fatality. Mosquito saliva can facilitate pathogen infection by downregulating the host's immune response.

D7 long salivary proteins modulate blood feeding and parasite infection.

During blood feeding, mosquitoes inject saliva into the host skin, preventing hemostasis and inflammatory responses. D7 proteins are among the most abundant components of the saliva of blood-feeding arthropods. , the vector of yellow fever and dengue, expresses two D7 long-form salivary proteins: D7L1 and D7L2.

Guianensin, a salivary protein, has broad anti-hemostatic and anti-inflammatory properties.

Background: Salivary glands from blood-feeding arthropods secrete several molecules that inhibit mammalian hemostasis and facilitate blood feeding and pathogen transmission. The salivary functions from , the main vector of Onchocerciasis in South America, remain largely understudied. Here, we have characterized a salivary protease inhibitor (Guianensin) from the blackfly .

The direct binding of AMA1 to erythrocytes defines a RON2-independent invasion pathway.

We used a transgenic parasite in which parasites were genetically modified to express apical membrane antigen 1 (PvAMA1) protein in place of PfAMA1 to study PvAMA1-mediated invasion. In , AMA1 interaction with rhoptry neck protein 2 (RON2) is known to be crucial for invasion, and PfRON2 peptides (PfRON2p) blocked the invasion of PfAMA1 wild-type parasites. However, PfRON2p has no effect on the invasion of transgenic parasites expressing PvAMA1 indicating that PfRON2 had no role in the invasion of PvAMA1 transgenic parasites.

Alboserpin, the Main Salivary Anticoagulant from the Disease Vector , Displays Anti-FXa-PAR Signaling In Vitro and In Vivo.

Blood-feeding arthropods secrete potent salivary molecules, which include platelet aggregation inhibitors, vasodilators, and anticoagulants. Among these molecules, Alboserpin, the major salivary anticoagulant from the mosquito vector , is a specific inhibitor of the human coagulation factor Xa (FXa). In this study, we investigated the anti-inflammatory properties of Alboserpin, in vitro and in vivo.

Novel salivary antihemostatic activities of long-form D7 proteins from the malaria vector Anopheles gambiae facilitate hematophagy.

To successfully feed on blood, hematophagous arthropods must combat the host's natural hemostatic and inflammatory responses. Salivary proteins of blood-feeding insects such as mosquitoes contain compounds that inhibit these common host defenses against blood loss, including vasoconstriction, platelet aggregation, blood clotting, pain, and itching. The D7 proteins are some of the most abundantly expressed proteins in female mosquito salivary glands and have been implicated in inhibiting host hemostatic and inflammatory responses.

Aedes aegypti sialokinin facilitates mosquito blood feeding and modulates host immunity and vascular biology.

Saliva from mosquitoes contains vasodilators that antagonize vasoconstrictors produced at the bite site. Sialokinin is a vasodilator present in the saliva of Aedes aegypti. Here, we investigate its function and describe its mechanism of action during blood feeding.

Piwi4 Structural Features Are Necessary for RNA Binding and Nuclear Localization.

The PIWI-interacting RNA (piRNA) pathway provides an RNA interference (RNAi) mechanism known from studies to maintain the integrity of the germline genome by silencing transposable elements (TE). mosquitoes, which are the key vectors of several arthropod-borne viruses, exhibit an expanded repertoire of Piwi proteins involved in the piRNA pathway, suggesting functional divergence. Here, we investigate RNA-binding dynamics and subcellular localization of Piwi4 (AePiwi4), a Piwi protein involved in antiviral immunity and embryonic development, to better understand its function.

The structures of two salivary proteins from the West Nile vector reveal a beta-trefoil fold with putative sugar binding properties.

Female mosquitoes require blood meals for egg development. The saliva of blood feeding arthropods contains biochemically active molecules, whose anti-hemostatic and anti-inflammatory properties facilitate blood feeding on vertebrate hosts. While transcriptomics has presented new opportunities to investigate the diversity of salivary proteins from hematophagous arthropods, many of these proteins remain functionally undescribed.

Inflammasome Fuels Dengue Severity.

Dengue is an acute febrile disease triggered by dengue virus. Dengue is the widespread and rapidly transmitted mosquito-borne viral disease of humans. Diverse symptoms and diseases due to Dengue virus (DENV) infection ranges from dengue fever, dengue hemorrhagic fever (life-threatening) and dengue shock syndrome characterized by shock, endothelial dysfunction and vascular leakage.

D7 Salivary Protein Prevents Host Hemostasis and Inflammation.

Mosquitoes inject saliva into the host skin to facilitate blood meal acquisition through active compounds that prevent hemostasis. D7 proteins are among the most abundant components of the mosquito saliva and act as scavengers of biogenic amines and eicosanoids. Several members of the D7 family have been characterized at the biochemical level; however, none have been studied thus far in , a permissive vector for several arboviruses that causes extensive human morbidity and mortality.

Biochemical characterization of AeD7L2 and its physiological relevance in blood feeding in the dengue mosquito vector, Aedes aegypti.

Aedes aegypti saliva facilitates blood meal acquisition through pharmacologically active compounds that prevent host hemostasis. Among these salivary proteins are the D7s, which are highly abundant and have been shown to act as scavengers of biogenic amines and eicosanoids. In this work, we performed comparative structural modeling, characterized the binding capabilities, and assessed the physiological functions of the Ae.

ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals.

During blood-feeding, mosquito saliva is injected into the skin to facilitate blood meal acquisition. D7 proteins are among the most abundant components of the mosquito saliva. Here we report the ligand binding specificity and physiological relevance of two D7 long proteins from Culex quinquefasciatus mosquito, the vector of filaria parasites or West Nile viruses.