{"doi":"10.1371/journal.pone.0229570","title":"Herpes simplex virus type 1 inflammasome activation in proinflammatory human macrophages is dependent on NLRP3, ASC, and caspase-1","abstract":"The proinflammatory cytokines interleukin (IL)-1β and IL-18 are products of activation of the inflammasome, an innate sensing system, and important in the pathogenesis of herpes simplex virus type 1 (HSV-1). The release of IL-18 and IL-1β from monocytes/macrophages is critical for protection from HSV-1 based on animal models of encephalitis and genital infection, yet if and how HSV-1 activates inflammasomes in human macrophages is unknown. To investigate this, we utilized both primary human monocyte derived macrophages and human monocytic cell lines (THP-1 cells) with various inflammasome components knocked-out. We found that HSV-1 activates inflammasome signaling in proinflammatory primary human macrophages, but not in resting macrophages. Additionally, HSV-1 inflammasome activation in THP-1 cells is dependent on nucleotide-binding domain and leucine-rich repeat-containing receptor 3 (NLRP3), apoptosis-associated speck-like molecule containing a caspase recruitment domain (ASC), and caspase-1, but not on absent in melanoma 2 (AIM2), or gamma interferon-inducible protein 16 (IFI16). In contrast, HSV-1 activates non-canonical inflammasome signaling in proinflammatory macrophages that results in IL-1β, but not IL-18, release that is independent of NLRP3, ASC, and caspase-1. Ultraviolet irradiation of HSV-1 enhanced inflammasome activation, demonstrating that viral replication suppresses inflammasome activation. These results confirm that HSV-1 is capable of activating the inflammasome in human macrophages through an NLRP3 dependent process and that the virus has evolved an NLRP3 specific mechanism to inhibit inflammasome activation in macrophages.","journal":"PLoS ONE","year":2020,"id":67001,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":355239,"name":"Alexis Figueroa","orcid":"0000-0002-6549-3489","position":1,"is_corresponding":false},{"id":278649,"name":"Guido Massaccesi","orcid":"0000-0002-4528-0937","position":2,"is_corresponding":false},{"id":357152,"name":"Sara Botto","orcid":null,"position":3,"is_corresponding":false},{"id":357153,"name":"Victor R. DeFilippis","orcid":null,"position":4,"is_corresponding":false},{"id":355240,"name":"Andrea L. Cox","orcid":"0000-0002-9331-2462","position":5,"is_corresponding":false},{"id":355238,"name":"Andrew H. Karaba","orcid":"0000-0003-2785-317X","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T21:15:12.020735Z","pmid":"32101570","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":[]}