{"doi":"10.1167/iovs.66.12.16","title":"Antagonizing Viral MicroRNAs Reduces Ocular HSV-1 Pathogenesis and Enhances Mucosal Immune Homeostasis","abstract":"Purpose: Herpes simplex virus 1 (HSV-1) is a globally prevalent pathogen that causes recurrent lesions at mucosal and cutaneous sites, including the cornea, leading to herpetic keratitis, a major cause of infectious blindness. While HSV-1-encoded microRNAs (v-miRs) are known to regulate viral latency and immune evasion, their role in acute mucosal infection remains unclear. This study investigates the function of v-miRs during acute HSV-1 infection of the cornea. Methods: Using a murine model of corneal HSV-1 infection, we performed RNA sequencing and in situ hybridization to identify v-miRs enriched in the cornea during acute infection. Topical locked nucleic acid (LNA)-modified inhibitors targeting individual v-miRs (miR-H1-5p, miR-H3-3p, miR-H6-3p, and miR-H27) were administered, and effects on disease severity, viral replication, immune response, and lymphoid cell activation were assessed. Results: Inhibition of select v-miRs significantly attenuated corneal keratitis, reduced viral titers, and suppressed Th1/Th17-mediated inflammation. v-miR inhibition also decreased immune cell infiltration in draining lymph nodes and enhanced the frequency of IL-10-producing CD4⁺ T cells. Expression of immunoregulatory genes, including Arg1 and CD25, was increased, and T-cell proliferation was reduced ex vivo, indicating the establishment of a tissue-protective immune environment. Conclusions: HSV-1 v-miRs act as key immunoregulatory effectors during acute corneal infection. Their targeted inhibition using LNA-based therapy mitigates inflammation and promotes immune regulation, highlighting a novel therapeutic strategy for ocular HSV-1 disease.","journal":"Investigative Ophthalmology & Visual Science","year":2025,"id":522008,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"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":459933,"name":"Raza Ali Naqvi","orcid":"0000-0003-0187-2081","position":1,"is_corresponding":false},{"id":1095801,"name":"Hemant P. Borase","orcid":"0000-0003-2097-1018","position":2,"is_corresponding":false},{"id":344185,"name":"Araceli Valverde","orcid":"0000-0001-6044-0209","position":3,"is_corresponding":false},{"id":344186,"name":"Afsar R. Naqvi","orcid":"0000-0001-7436-3056","position":4,"is_corresponding":false},{"id":286249,"name":"Deepak Shukla","orcid":"0000-0002-3039-6953","position":5,"is_corresponding":false},{"id":286248,"name":"Chandrashekhar D. Patil","orcid":"0000-0002-5641-4523","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:49.198144Z","pmid":"40910727","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":[]}