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Journal of General Virology header logo Journal of General Virology

Volume 107, Issue 3

Optimization of lytic herpes simplex virus infection in human induced pluripotent stem cell-derived cortical neurones Open Access

Abstract

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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): herpes simplex encephalitis (HSE) , i3Neurones , neurones and virus–host interactions
Funding
This study was supported by the:
  • Wellcome Trust (Award 219447/Z/19/Z)
    • Principal Award Recipient: JanetE. Deane
© 2026 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2026-03-07

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Optimization of lytic herpes simplex virus infection in human induced pluripotent stem cell-derived cortical neurones
J. Gen. Virol. 107, 002237 (2026); https://doi.org/10.1099/jgv.0.002237
/content/journal/jgv/10.1099/jgv.0.002237
/content/journal/jgv/10.1099/jgv.0.002237
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