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

Viruses

Sibylle Widéhn¹  Tomas Bergström¹  Charlotta E. Eriksson¹  Maria Johansson¹  Edward Trybala¹  Tugce Munise Satir²  Stefanie Fruhwürth²  Petra Bergström²  Faisal Hayat Nazir²  Lotta Agholme²  Henrik Zetterberg³  Wojciech Michno³  Jörg Hanrieder³  Soren Riis Paludan⁴ 

[1] Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden;Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden;Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-431 80 Mölndal, Sweden;Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden;

关键词: herpes simplex virus;    human induced pluripotent stem cells;    human neuroprogenitors;    central nervous system infection;    cortical neurons;   

DOI  :  10.3390/v13102072

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown