{"doi":"10.17615/tthm-9674","title":"Proteasomal Degradation of Herpes Simplex Virus Capsids in Macrophages Releases DNA to the Cytosol for Recognition by DNA Sensors","abstract":"The innate immune system is important for control of infections, including herpesvirus infections. Intracellular DNA potently stimulates antiviral IFN responses. It is known that plasmacytoid dendritic cells sense herpesvirus DNA in endosomes via TLR9, and that non-immune tissue cells can sense herpesvirus DNA in the nucleus. However, it remains unknown how and where myeloid cells, like macrophages and conventional dendritic cells, detect infections with herpesviruses. Here we demonstrate that the HSV-1 capsid was ubiquitinated in the cytosol and degraded by the proteasome, hence releasing genomic DNA into the cytoplasm for detection by DNA sensors. In this context, the DNA sensor IFI16 is important for induction of IFN-β in human macrophages after infection with HSV-1 and CMV. Viral DNA localized to the same cytoplasmic regions as IFI16, with DNA sensing being independent of viral nuclear entry. Thus, proteasomal degradation of herpesvirus capsids releases DNA to the cytoplasm for recognition by DNA sensors.","journal":"UNC Libraries","year":2020,"id":144049,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":256461,"name":"Evelyn A. Kurt‐Jones","orcid":"0000-0003-4669-2084","position":1,"is_corresponding":false},{"id":612564,"name":"Jesper Melchjorsen","orcid":null,"position":2,"is_corresponding":false},{"id":612068,"name":"Marie B. Iversen","orcid":"0000-0001-7335-6436","position":3,"is_corresponding":false},{"id":612069,"name":"Kristy Horan","orcid":"0000-0003-3960-1519","position":4,"is_corresponding":false},{"id":612565,"name":"Kathrine Hansen","orcid":null,"position":5,"is_corresponding":false},{"id":612070,"name":"Christian K. Holm","orcid":"0000-0002-2655-3362","position":6,"is_corresponding":false},{"id":263811,"name":"Blossom Damania","orcid":"0000-0002-9205-1774","position":7,"is_corresponding":false},{"id":612071,"name":"Leonie Unterholzner","orcid":"0000-0001-9824-692X","position":8,"is_corresponding":false},{"id":38070,"name":"Søren R. Paludan","orcid":"0000-0001-9180-4060","position":9,"is_corresponding":false},{"id":612072,"name":"Santo Landolfo","orcid":"0000-0002-3153-2865","position":10,"is_corresponding":false},{"id":612073,"name":"Andrew Bowie","orcid":"0000-0001-5316-4373","position":11,"is_corresponding":false},{"id":612074,"name":"Simon Rasmussen","orcid":"0000-0001-6323-9041","position":12,"is_corresponding":false},{"id":350103,"name":"Martin R. Jakobsen","orcid":"0000-0001-8847-9201","position":13,"is_corresponding":false},{"id":612566,"name":"Mikayla Thompson","orcid":null,"position":14,"is_corresponding":false},{"id":109691,"name":"Katherine A. Fitzgerald","orcid":"0000-0003-3175-609X","position":15,"is_corresponding":false},{"id":612567,"name":"Stine Søby","orcid":null,"position":16,"is_corresponding":false},{"id":529610,"name":"John A. West","orcid":null,"position":17,"is_corresponding":false},{"id":612067,"name":"Svend Ellermann‐Eriksen","orcid":"0000-0001-9324-911X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:41.821196Z","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":[]}