{"doi":"10.1371/journal.pntd.0010743","title":"Identification of Aedes aegypti salivary gland proteins interacting with human immune receptor proteins","abstract":"<jats:p>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<jats:italic>Ae</jats:italic>.<jats:italic>aegypti</jats:italic>salivary gland proteins (SGPs) (e.g., apyrase,<jats:italic>Ae</jats:italic>.<jats:italic>aegypti</jats:italic>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<jats:italic>Ae</jats:italic>.<jats:italic>aegypti</jats:italic>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<jats:sup>+</jats:sup>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.</jats:p>","journal":"PLOS Neglected Tropical Diseases","year":2022,"id":643782,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1107505,"name":"Yeu Khai Choong","orcid":"0000-0002-2868-3929","position":1,"is_corresponding":false},{"id":1675220,"name":"Yonghao Liu","orcid":null,"position":2,"is_corresponding":false},{"id":895167,"name":"Julien Pompon","orcid":"0000-0003-1110-9039","position":3,"is_corresponding":false},{"id":603238,"name":"Eng Eong Ooi","orcid":"0000-0002-0520-1544","position":4,"is_corresponding":false},{"id":1675221,"name":"Yu Keung Mok","orcid":null,"position":5,"is_corresponding":false},{"id":413670,"name":"Haiyan Liu","orcid":"0000-0002-2500-4601","position":6,"is_corresponding":false},{"id":126961,"name":"R Manjunatha Kini","orcid":null,"position":7,"is_corresponding":false},{"id":1411686,"name":"J. Sivaraman","orcid":"0000-0001-9781-5326","position":8,"is_corresponding":false},{"id":1396999,"name":"Edem Gavor","orcid":"0000-0001-7100-7849","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Identification of Aedes aegypti salivary gland proteins interacting with human immune receptor proteins","abstract":"<jats:p>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<jats:italic>Ae</jats:italic>.<jats:italic>aegypti</jats:italic>salivary gland proteins (SGPs) (e.g., apyrase,<jats:italic>Ae</jats:italic>.<jats:italic>aegypti</jats:italic>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<jats:italic>Ae</jats:italic>.<jats:italic>aegypti</jats:italic>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<jats:sup>+</jats:sup>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.</jats:p>","is_dataset_classified":null,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36070318","pmcid":"PMC9484696","openalex_id":"https://openalex.org/W4294884753","authors":[],"funders":[{"funder_name":"Ministry of Education - Singapore","grant_id":"R154-000-697-112","title":null},{"funder_name":"Ministry of Education - Singapore","grant_id":"R154-000-C07-114","title":null}],"total_grants":2,"fwci":3.4887,"citation_percentile":0.9293431,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":10},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0010743&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0010743&type=printable","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pntd.0010743","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pntd.0010743","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36070318","host_type":"repository"},{"url":"https://hal.science/hal-03877100","host_type":"repository"},{"url":"https://doaj.org/article/95f02715ee0e49d99342b9a0e1dd98e1","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9484696","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9484696","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9484696?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Mosquito-borne diseases and control","Vector-borne infectious diseases","Food Allergy and Anaphylaxis Research","Aedes","Allergens","Animals","Apyrase","Humans","Intercellular Adhesion Molecule-3","Mosquito Vectors","Recombinant Proteins","Salivary Proteins and Peptides","Toll-Like Receptor 4"],"mesh_terms":["Mosquito Vectors","Intercellular Adhesion Molecule-3","Aedes","Allergens","Animals","Apyrase","Humans","Recombinant Proteins","Salivary Proteins and Peptides","Toll-Like Receptor 4"],"keywords":["Biology","Aedes aegypti","Immune system","Innate immune system","Receptor","Virology","Cell biology","Microbiology","Immunology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T18:52:27.353647Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}