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

Autor: Gavor E; Department of Biological Sciences, National University of Singapore, Singapore., Choong YK; Department of Biological Sciences, National University of Singapore, Singapore., Liu Y; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Immunology Programme, Life Sciences Institute, Immunology Translational Research Program and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Pompon J; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.; MIVEGEC, University of Montpellier, IRD, CNRS, Montpellier, France., Ooi EE; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore., Mok YK; Department of Biological Sciences, National University of Singapore, Singapore., Liu H; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Immunology Programme, Life Sciences Institute, Immunology Translational Research Program and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Kini RM; Department of Biological Sciences, National University of Singapore, Singapore.; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Sivaraman J; Department of Biological Sciences, National University of Singapore, Singapore.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2022 Sep 07; Vol. 16 (9), pp. e0010743. Date of Electronic Publication: 2022 Sep 07 (Print Publication: 2022).
DOI: 10.1371/journal.pntd.0010743
Abstrakt: Mosquito saliva proteins modulate the human immune and hemostatic systems and control mosquito-borne pathogenic infections. One mechanism through which mosquito proteins may influence host immunity and hemostasis is their interactions with key human receptor proteins that may act as receptors for or coordinate attacks against invading pathogens. Here, using pull-down assays and proteomics-based mass spectrometry, we identified 11 Ae. aegypti salivary gland proteins (SGPs) (e.g., apyrase, Ae. aegypti venom allergen-1 [AaVA-1], neutrophil stimulating protein 1 [NeSt1], and D7 proteins), that interact with one or more of five human receptor proteins (cluster of differentiation 4 [CD4], CD14, CD86, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN], and Toll-like receptor 4 [TLR4]). We focused on CD4- and DC-SIGN-interacting proteins and confirmed that CD4 directly interacts with AaVA-1, D7, and NeST1 recombinant proteins and that AaVA-1 showed a moderate interaction with DC-SIGN using ELISA. Bacteria responsive protein 1 (AgBR1), an Ae. aegypti saliva protein reported to enhance ZIKV infection in humans but that was not identified in our pull-down assay moderately interacts with CD4 in the ELISA assay. Functionally, we showed that AaVA-1 and NeST1 proteins promoted activation of CD4+ T cells. We propose the possible impact of these interactions and effects on mosquito-borne viral infections such as dengue, Zika, and chikungunya viruses. Overall, this study provides key insight into the vector-host (protein-protein) interaction network and suggests roles for these interactions in mosquito-borne viral infections.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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