{"doi":"10.1073/pnas.2413965122","title":"Co-option of mitochondrial nucleic acid–sensing pathways by HSV-1 UL12.5 for reactivation from latent infection","abstract":"Although viruses subvert innate immune pathways for their replication, there is evidence they can also co-opt antiviral responses for their benefit. The ubiquitous human pathogen, Herpes simplex virus-1 (HSV-1), encodes a protein (UL12.5) that induces the release of mitochondrial nucleic acid into the cytosol, which activates immune-sensing pathways and reduces productive replication in nonneuronal cells. HSV-1 establishes latency in neurons and can reactivate to cause disease. We found that UL12.5 is required for HSV-1 reactivation in neurons and acts to directly promote viral lytic gene expression during initial exit from latency. Further, the direct activation of innate immune-sensing pathways triggered HSV-1 reactivation and compensated for a lack of UL12.5. Finally, we found that the induction of HSV-1 lytic genes during reactivation required intact RNA- and DNA-sensing pathways, demonstrating that HSV-1 can respond to and active antiviral nucleic acid-sensing pathways to reactivate from a latent infection.","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":537903,"datarank":0.2751852564211242,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.03376956955600909,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.03376956955600909,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":4,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1424130,"name":"M. Flores","orcid":"0009-0009-4267-7718","position":1,"is_corresponding":false},{"id":686619,"name":"Sean R. Cuddy","orcid":"0000-0001-8926-4077","position":2,"is_corresponding":false},{"id":947733,"name":"Abigail L. Whitford","orcid":null,"position":3,"is_corresponding":false},{"id":570015,"name":"Sara A. Dochnal","orcid":"0000-0003-3011-567X","position":4,"is_corresponding":false},{"id":686621,"name":"Aleksandra Babnis","orcid":"0000-0003-1714-4003","position":5,"is_corresponding":false},{"id":461008,"name":"Tsuyoshi Miyake","orcid":"0009-0008-3134-3205","position":6,"is_corresponding":false},{"id":1169699,"name":"Marco Tigano","orcid":"0000-0002-4353-9220","position":7,"is_corresponding":false},{"id":462409,"name":"Daniel A. Engel","orcid":null,"position":8,"is_corresponding":false},{"id":570017,"name":"Anna R. Cliffe","orcid":"0000-0003-1136-5171","position":9,"is_corresponding":false},{"id":1174018,"name":"Patryk A. Krakowiak","orcid":"0000-0002-5120-9811","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:16.891390Z","pmid":"39854226","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":[]}