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<p>Influenza A virus (IAV) infection is associated with a wide variety of neurological complications, of which mild complications like impaired cognitive functioning are most prominent. Even though several studies have shown that many influenza viruses can enter the CNS, the neuropathogenesis of seasonal (H3N2 and H1N1) and pandemic (pH1N1 2009) IAV infections is poorly understood. Therefore, we aimed to investigate the cellular tropism, replication efficiency and associated functional consequences using a human stem cell-derived neural co-culture model of neurons and astrocytes. All viruses were able to infect neurons in the co-culture model, although this infection did not result in efficient replication and release of progeny virus. In addition, infection did not result in visible cell death or apoptosis. However, functional analyses revealed that IAV inoculation resulted in a reduction of spontaneous neural activity and a partial reduction of neural excitability. This study shows that seasonal and pandemic IAVs can disrupt neural homeostasis, without efficient virus replication or the induction of cell death. These functional changes in neural activity can contribute to cognitive problems during IAV infections in the acute and potentially post-acute phase of the infection.</p>

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Influenza A virus infection impairs neuronal activity in human iPSC-derived NGN2 neural co-cultures

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月18日

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  • Feline F. W. Benavides,
  • Annabel L. V. Kempff,
  • Hilde Smeenk,
  • Bas Lendemeijer,
  • Marla Lavrijsen,
  • Johan A. Slotman,
  • Steven A. Kushner,
  • Femke M. S. de Vrij,
  • Lisa Bauer,
  • Debby van Riel

摘要

Influenza A virus (IAV) infection is associated with a wide variety of neurological complications, of which mild complications like impaired cognitive functioning are most prominent. Even though several studies have shown that many influenza viruses can enter the CNS, the neuropathogenesis of seasonal (H3N2 and H1N1) and pandemic (pH1N1 2009) IAV infections is poorly understood. Therefore, we aimed to investigate the cellular tropism, replication efficiency and associated functional consequences using a human stem cell-derived neural co-culture model of neurons and astrocytes. All viruses were able to infect neurons in the co-culture model, although this infection did not result in efficient replication and release of progeny virus. In addition, infection did not result in visible cell death or apoptosis. However, functional analyses revealed that IAV inoculation resulted in a reduction of spontaneous neural activity and a partial reduction of neural excitability. This study shows that seasonal and pandemic IAVs can disrupt neural homeostasis, without efficient virus replication or the induction of cell death. These functional changes in neural activity can contribute to cognitive problems during IAV infections in the acute and potentially post-acute phase of the infection.