{"doi":"10.3390/pathogens14080823","title":"Acute HSV-1 Ocular Infection Is Impaired in KLF15 Knockout Mice but Stress-Induced Reactivation from Latency Is Prolonged in Male KLF15 Knockout Mice","abstract":"Acute human alpha-herpesvirus 1 (HSV-1) infection culminates in a latent infection of neurons in trigeminal ganglia (TG) and the central nervous system. Following infection of mucosal epithelial cells, certain neurons survive infection and life-long latency is established. Periodically, stressful stimuli trigger reactivation from latency, which result in virus shedding, transmission to other people, and, occasionally, recurrent disease. The glucocorticoid receptor (GR) and Krüppel-like factor 15 (KLF15) comprise a feed-forward transcriptional loop that cooperatively transactivate key HSV-1 promoters that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. Silencing KLF15 significantly reduces HSV-1 replication in cultured mouse neuroblastoma cells. Consequently, we hypothesized that KLF15 mediates certain aspects of reactivation from latency. To test this hypothesis, we compared HSV-1 replication in KLF15−/− mice versus wild-type (wt) parental C57BL/6 mice. Virus shedding during acute infection was reduced in KLF15−/− mice. Male KLF15−/− mice shed higher titers of virus during late stages of reactivation from latency compared to KLF15−/− females and wt mice regardless of sex. At 15 d after explant-induced reactivation, virus shedding was higher in male KLF15−/− mice relative to wt mice and female KLF15−/− mice. These studies confirm KLF15 expression enhances viral replication during acute infection and reactivation from latency.","journal":"Pathogens","year":2025,"id":546254,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"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":400695,"name":"Clinton Jones","orcid":"0000-0002-6656-4971","position":1,"is_corresponding":false},{"id":402433,"name":"Kelly S. Harrison","orcid":"0000-0003-0211-8769","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:53:32.285899Z","pmid":"40872334","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":[]}