{"doi":"10.1101/2023.05.31.543096","title":"<i>Wolbachia</i> -induced inhibition of O’nyong nyong virus in <i>Anopheles</i> mosquitoes is mediated by Toll signaling and modulated by cholesterol","abstract":"ABSTRACT Enhanced host immunity and competition for metabolic resources are two main competing hypotheses for the mechanism of Wolbachia -mediated pathogen inhibition in arthropods. Using an Anopheles mosquito – somatic Wolbachia infection – O’nyong nyong virus (ONNV) model, we demonstrate that the mechanism underpinning Wolbachia -mediated virus inhibition is up-regulation of the Toll innate immune pathway. However, the viral inhibitory properties of Wolbachia were abolished by cholesterol supplementation. This result was due to Wolbachia -dependent cholesterol-mediated suppression of Toll signaling rather than competition for cholesterol between Wolbachia and virus. The inhibitory effect of cholesterol was specific to Wolbachia -infected Anopheles mosquitoes and cells. These data indicate that both Wolbachia and cholesterol influence Toll immune signaling in Anopheles mosquitoes in a complex manner and provide a functional link between the host immunity and metabolic competition hypotheses for explaining Wolbachia -mediated pathogen interference in mosquitoes. In addition, these results provide a mechanistic understanding of the mode of action of Wolbachia -induced pathogen blocking in Anophelines, which is critical to evaluate the long-term efficacy of control strategies for malaria and Anopheles -transmitted arboviruses. HIGHLIGHTS Wolbachia inhibits O’nyong nyong virus (ONNV) in Anopheles mosquitoes. Enhanced Toll signaling is responsible for Wolbachia -induced interference of ONNV. Cholesterol suppresses Toll signaling to modulate Wolbachia -induced ONNV interference.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393325,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230622,"name":"Grant L. Hughes","orcid":"0000-0002-7567-7185","position":1,"is_corresponding":false},{"id":1167164,"name":"Nazzy Pakpour","orcid":"0000-0002-1148-7294","position":2,"is_corresponding":false},{"id":115403,"name":"Yasutsugu Suzuki","orcid":"0000-0002-8202-3032","position":3,"is_corresponding":false},{"id":275640,"name":"Jason L. Rasgon","orcid":"0000-0002-4050-8429","position":4,"is_corresponding":false},{"id":292321,"name":"Sujit Pujhari","orcid":"0000-0001-5856-5328","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:01.355412Z","pmid":"37397989","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":[]}