{"doi":"10.1371/journal.pone.0307450","title":"RNA editing regulates host immune response and T cell homeostasis in SARS-CoV-2 infection","abstract":"Adenosine to inosine (A-to-I) RNA editing by ADAR1 has been implicated in maintaining self-tolerance, preventing autoimmunity, and mediating antiviral immunity. Foreign viral double-stranded RNA triggers rapid interferon response and activates ADAR1 in the host immune system. Emerging data points to a role of ADAR1 A-to-I editing in the inflammatory response associated with severe COVID-19 disease. We identify A-to-I editing events within human whole transcriptome data from SARS-CoV-2 infected individuals, non-infected individuals, and individuals with other viral illnesses from nasopharyngeal swabs. High levels of RNA editing in host cells are associated with low SARS-CoV-2 viral load (p = 9.27 E-06), suggesting an inhibitory effect of ADAR1 on viral infection. Additionally, we find differentially expressed genes associated with RNA-modifications and interferon response. Single cell RNA-sequencing analysis of SARS-CoV-2 infected nasopharyngeal swabs reveals that cytotoxic CD8 T cells upregulate ADAR1 in COVID-19 positive samples (p = 0.0269). We further reveal ADAR1 expression increases with CD4 and CD8 T cell activation, and knockdown of ADAR1 leads to apoptosis and aberrant IL-2 secretion. Together, our data suggests A-to-I RNA editing is required to maintain healthy homeostasis of activated T cells to combat SARS-CoV-2 infection.","journal":"PLoS ONE","year":2024,"id":456372,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":398125,"name":"Adam Mark","orcid":"0000-0003-4037-9572","position":1,"is_corresponding":false},{"id":666848,"name":"Jessica Pham","orcid":"0000-0002-4837-6379","position":2,"is_corresponding":false},{"id":1280796,"name":"Karina Vera","orcid":"0000-0003-2669-4285","position":3,"is_corresponding":false},{"id":37867,"name":"Amanda Saravia-Butler","orcid":"0000-0001-7505-2743","position":4,"is_corresponding":false},{"id":37850,"name":"Afshin Beheshti","orcid":"0000-0003-4643-531X","position":5,"is_corresponding":false},{"id":103666,"name":"Sara Brin Rosenthal","orcid":"0000-0002-9072-8032","position":6,"is_corresponding":false},{"id":12597,"name":"Kathleen M. Fisch","orcid":"0000-0002-0117-7444","position":7,"is_corresponding":false},{"id":1281245,"name":"Molly Huang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:03:27.785212Z","pmid":"39178184","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":[]}