A salivary protein of Aedes aegypti promotes dengue-2 virus replication and transmission

Sri-in, Chalida; Weng, Shih-Che; Chen, Wenyu; Wu-Hsieh, Betty A.; Tu, Wu‐Chun; Shiao, Shin-Hong

doi:10.1016/j.ibmb.2019.103181

Cited by 28 publications

(55 citation statements)

References 34 publications

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“…The physiological role of the 34 kDa and 62 kDa salivary proteins in blood feeding is presently unknown, however the 34k1 Ae . aegypti protein was found to enhance DENV replication in human keratinocytes [56] and its silencing in the mosquito by RNAi reduced DENV2 replication in the salivary glands [57]. The first peptide, alb34k1-P1 (21 amino acids) is designed on the N-terminus of the Ae .…”

Section: Resultsmentioning

confidence: 99%

Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from Aedes albopictus and Aedes aegypti as novel promising candidate markers of host exposure to Aedes mosquitoes

Montero¹,

Gabrieli

Severini

et al. 2019

PLoS Negl Trop Dis

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BackgroundAedes mosquitoes are vectors of arboviral diseases of great relevance for public health. The recent outbreaks of dengue, Zika, chikungunya and the rapid worldwide spreading of Aedes albopictus emphasize the need for improvement of vector surveillance and control. Host antibody response to mosquito salivary antigens is emerging as a relevant additional tool to directly assess vector-host contact, monitor efficacy of control interventions and evaluate risk of arboviral transmission.Methodology/principal findingsGroups of four BALB/c mice were immunized by exposure to bites of either Aedes albopictus or Aedes aegypti. The 34k2 salivary proteins from Ae. albopictus (al34k2) and Ae. aegypti (ae34k2) were expressed in recombinant form and Ae. albopictus salivary peptides were designed through B-cell epitopes prediction software. IgG responses to salivary gland extracts, peptides, al34k2 and ae34k2 were measured in exposed mice. Both al34k2 and ae34k2, with some individual and antigen-specific variation, elicited a clearly detectable antibody response in immunized mice. Remarkably, the two orthologous proteins showed very low level of immune cross-reactivity, suggesting they may eventually be developed as species-specific markers of host exposure. The al34k2 immunogenicity and the limited immune cross-reactivity to ae34k2 were confirmed in a single human donor hyperimmune to Ae. albopictus saliva.Conclusions/significanceOur study shows that exposure to bites of Ae. albopictus or Ae. aegypti evokes in mice species-specific IgG responses to al34k2 or ae34k2, respectively. Deeper understanding of duration of antibody response and validation in natural conditions of human exposure to Aedes mosquitoes are certainly needed. However, our findings point to the al34k2 salivary protein as a promising potential candidate for the development of immunoassays to evaluate human exposure to Ae. albopictus. This would be a step forward in the establishment of a serological toolbox for the simultaneous assessment of human exposure to Aedes vectors and the pathogens they transmit.

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Section: Resultsmentioning

confidence: 99%

Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from Aedes albopictus and Aedes aegypti as novel promising candidate markers of host exposure to Aedes mosquitoes

Montero¹,

Gabrieli

Severini

et al. 2019

PLoS Negl Trop Dis

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“…DENV-2 (NGC strain) has been reported to be particularly virulent and the cause of many severe dengue outbreaks ( Wang et al., 2016 ; Williams et al., 2014 ; Yung et al., 2015 ). Most research articles ( Molina-Cruz et al, 2005 , Salazar et al, 2007 , Sanchez-Vargas et al, 2018 , Sri-In et al, 2019 , Tree et al, 2019 ) have used DENV-2 for proof-of-principle experiments. Here we utilized DENV-2 NGC, the most commonly used strain.…”

Section: Discussionmentioning

confidence: 99%

C-Type Lectins Link Immunological and Reproductive Processes in Aedes aegypti

Cai

et al. 2020

iScience

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Summary Physiological trade-offs between mosquito immune response and reproductive capability can arise due to insufficient resource availability. C-type lectin family members may be involved in these processes. We established a GCTL-3 −/− mutant Aedes aegypti using CRISPR/Cas9 to investigate the role of GCTL-3 in balancing the costs associated with immune responses to arboviral infection and reproduction. GCTL-3 −/− mutants showed significantly reduced DENV-2 infection rate and gut commensal microbiota populations, as well as upregulated JAK/STAT, IMD, Toll, and AMPs immunological pathways. Mutants also had significantly shorter lifespans than controls and laid fewer eggs due to defective germ line development. dsRNA knock-down of Attacin and Gambicin , two targets of the AMPs pathway, partially rescued this reduction in reproductive capabilities. Upregulation of immune response following GCTL-3 knock-out therefore comes at a cost to reproductive fitness. Knock-out of other lectins may further improve our knowledge of the molecular and genetic mechanisms underlying reproduction-immunity trade-offs in mosquitoes.

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“…The culture supernatant was harvested at 7 dpi and stored at −80°C. To determine the viral titer, the virus stock was subjected to examination with a plaque assay, as previously described ( 24 ). Approximately 1.0 × 10 7 PFU/mL DENV2 was used to infect the mosquitoes.…”

Section: Methodsmentioning

confidence: 99%

“…The plates were fixed with 4% formaldehyde for one hour at room temperature and stained with 1% crystal violet for 30 minutes. Plaques were quantified via manual counting ( 24 ).…”

Section: Methodsmentioning

confidence: 99%

A Thioester-Containing Protein Controls Dengue Virus Infection in Aedes aegypti Through Modulating Immune Response

Weng

et al. 2021

Front. Immunol.

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Complement-like proteins in arthropods defend against invading pathogens in the early phases of infection. Thioester-containing proteins (TEPs), which exhibit high similarity to mammalian complement C3, are thought to play a key role in the innate immunity of arthropods. We identified and characterized anti-dengue virus (DENV) host factors, in particular complement-like proteins, in the mosquito Aedes aegypti. Our results indicate that TEP1 limits DENV infection in Ae. aegypti. We showed that TEP1 transcription is highly induced in mosquitoes following DENV infection. Silencing TEP1 resulted in the up-regulation of viral RNA and proteins. In addition, the production of infectious virus particles increased in the absence of TEP1. We generated a transgenic mosquito line with a TEP1 loss-of-function phenotype under a blood meal-inducible promoter. We showed that viral protein and titers increased in transgenic mosquitoes after an infectious blood meal. Interestingly, expression of transcription factor Rel2 and certain anti-microbial peptides (AMPs) were inhibited in transgenic mosquitoes. Overall, our results suggest that TEP1 regulates the immune response and consequently controls the replication of dengue virus in mosquitoes. This finding provides new insight into the molecular mechanisms of mosquito host factors in the regulation of DENV replication.

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A salivary protein of Aedes aegypti promotes dengue-2 virus replication and transmission

Cited by 28 publications

References 34 publications

Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from Aedes albopictus and Aedes aegypti as novel promising candidate markers of host exposure to Aedes mosquitoes

Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from Aedes albopictus and Aedes aegypti as novel promising candidate markers of host exposure to Aedes mosquitoes

C-Type Lectins Link Immunological and Reproductive Processes in Aedes aegypti

A Thioester-Containing Protein Controls Dengue Virus Infection in Aedes aegypti Through Modulating Immune Response

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