{"doi":"10.1099/jgv.0.002237","title":"Optimization of lytic herpes simplex virus infection in human induced pluripotent stem cell-derived cortical neurones","abstract":"<jats:p>Herpes simplex virus (HSV)-1 infection of cortical neurones is a leading cause of encephalitis. Whilst we have substantial knowledge about the molecular virology of HSV-1 lytic infection in cells of the periphery, like keratinocytes or fibroblasts, we know much less about infection of human neurones owing to the challenges of working with neuronal cell-based models. Here, we demonstrate the use of a human induced pluripotent stem cell-derived cortical neurone model (i3Neurones) for HSV-1 infection. i3Neurones are highly scalable and can be rapidly and efficiently differentiated into an isogenic population of cortical glutamatergic neurones. We show that i3Neurones support the full HSV-1 lytic replication cycle. We present an optimized protocol for the infection of i3Neurones with HSV-1 that allows their synchronous infection at near-100% efficiency and optimized fixation methods that preserve organelle and neurite structure for immunocytochemistry analysis. Our study highlights i3Neurones as a robust, scalable platform for microscopy and biochemical studies of HSV-1 and other neurotropic pathogens.</jats:p>","journal":"Journal of General Virology","year":2026,"id":649106,"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":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1228211,"name":"Alex S. 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We show that i3Neurones support the full HSV-1 lytic replication cycle. We present an optimized protocol for the infection of i3Neurones with HSV-1 that allows their synchronous infection at near-100% efficiency and optimized fixation methods that preserve organelle and neurite structure for immunocytochemistry analysis. 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