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Article

Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons

1
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden
2
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden
3
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden
4
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-431 80 Mölndal, Sweden
5
Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK
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Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
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Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark
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UK Dementia Research Institute at University College London, London WC1E 6BT, UK
9
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, SE-431 80 Mölndal, Sweden
*
Author to whom correspondence should be addressed.
Academic Editor: Stephen A. Rice
Viruses 2021, 13(10), 2072; https://doi.org/10.3390/v13102072
Received: 9 September 2021 / Revised: 6 October 2021 / Accepted: 8 October 2021 / Published: 14 October 2021
(This article belongs to the Special Issue Replication and Spread of Alphaherpesviruses)
Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2. View Full-Text
Keywords: herpes simplex virus; human induced pluripotent stem cells; human neuroprogenitors; central nervous system infection; cortical neurons herpes simplex virus; human induced pluripotent stem cells; human neuroprogenitors; central nervous system infection; cortical neurons
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MDPI and ACS Style

Bergström, P.; Trybala, E.; Eriksson, C.E.; Johansson, M.; Satir, T.M.; Widéhn, S.; Fruhwürth, S.; Michno, W.; Nazir, F.H.; Hanrieder, J.; Paludan, S.R.; Agholme, L.; Zetterberg, H.; Bergström, T. Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons. Viruses 2021, 13, 2072. https://doi.org/10.3390/v13102072

AMA Style

Bergström P, Trybala E, Eriksson CE, Johansson M, Satir TM, Widéhn S, Fruhwürth S, Michno W, Nazir FH, Hanrieder J, Paludan SR, Agholme L, Zetterberg H, Bergström T. Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons. Viruses. 2021; 13(10):2072. https://doi.org/10.3390/v13102072

Chicago/Turabian Style

Bergström, Petra, Edward Trybala, Charlotta E. Eriksson, Maria Johansson, Tugce M. Satir, Sibylle Widéhn, Stefanie Fruhwürth, Wojciech Michno, Faisal H. Nazir, Jörg Hanrieder, Soren R. Paludan, Lotta Agholme, Henrik Zetterberg, and Tomas Bergström. 2021. "Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons" Viruses 13, no. 10: 2072. https://doi.org/10.3390/v13102072

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