{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:05:28Z","timestamp":1791443128524,"version":"4.3.3"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Research Foundation of Western Gotaland, Sweden","award":["#93420"],"award-info":[{"award-number":["#93420"]}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2018-02532"],"award-info":[{"award-number":["2018-02532"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2018-02463"],"award-info":[{"award-number":["2018-02463"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["681712"],"award-info":[{"award-number":["681712"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swedish State Support for Clinical Research","award":["ALFGBG-720931"],"award-info":[{"award-number":["ALFGBG-720931"]}]},{"name":"Swedish State Support for Clinical Research","award":["ALFGBG-71690"],"award-info":[{"award-number":["ALFGBG-71690"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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 &lt; 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.<\/jats:p>","DOI":"10.3390\/v13102072","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T23:02:16Z","timestamp":1634252536000},"page":"2072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons"],"prefix":"10.3390","volume":"13","author":[{"given":"Petra","family":"Bergstr\u00f6m","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Trybala","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0743-0399","authenticated-orcid":false,"given":"Charlotta E.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tugce Munise","family":"Satir","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"Wid\u00e9hn","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Fruhw\u00fcrth","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden"},{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-3604","authenticated-orcid":false,"given":"Wojciech","family":"Michno","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-431 80 M\u00f6lndal, Sweden"},{"name":"Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal Hayat","family":"Nazir","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden"},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-431 80 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Hanrieder","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-431 80 M\u00f6lndal, Sweden"},{"name":"Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soren Riis","family":"Paludan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden"},{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotta","family":"Agholme","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE-431 80 M\u00f6lndal, Sweden"},{"name":"Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK"},{"name":"UK Dementia Research Institute at University College London, London WC1E 6BT, UK"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, SE-431 80 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Bergstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 46 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6461","DOI":"10.1073\/pnas.78.10.6461","article-title":"Herpes simplex type 1 DNA in human brain tissue","volume":"78","author":"Fraser","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/ana.410360605","article-title":"Herpes simplex virus genomes in human nervous system tissue analyzed by polymerase chain reaction","volume":"36","author":"Baringer","year":"1994","journal-title":"Ann. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0928-0197(95)00203-0","article-title":"Detection of herpes simplex virus (types 1 and 2) and human herpesvirus 6 DNA in human brain tissue by polymerase chain reaction","volume":"6","author":"Gordon","year":"1996","journal-title":"Clin. Diagn. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1177\/0883073809353449","article-title":"Chronic active herpes simplex type 2 encephalitis in an asymptomatic immunocompetent child","volume":"25","author":"Brown","year":"2010","journal-title":"J. Child. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Nakajima, H., Tani, H., Kobayashi, T., and Kimura, F. (2014). Chronic herpes simplex virus type 2 encephalitis associated with posterior uveitis. BMJ Case Rep., 2014.","DOI":"10.1136\/bcr-2013-201586"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1136\/jnnp.48.4.297","article-title":"The limbic system and the localisation of herpes simplex encephalitis","volume":"48","author":"Damasio","year":"1985","journal-title":"J. Neurol. Neurosurg. Psy."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s13365-013-0158-x","article-title":"Herpes simplex virus 2 meningitis: A retrospective cohort study","volume":"19","author":"Miller","year":"2013","journal-title":"J. Neurovirol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/infdis\/162.2.322","article-title":"Primary and recurrent herpes simplex virus type 2-induced meningitis","volume":"162","author":"Bergstrom","year":"1990","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1086\/521262","article-title":"Herpes simplex encephalitis in Sweden, 1990\u20132001: Incidence, morbidity, and mortality","volume":"45","author":"Hjalmarsson","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1186\/s13054-015-1046-y","article-title":"Long-term outcome of severe herpes simplex encephalitis: A population-based observational study","volume":"19","author":"Jouan","year":"2015","journal-title":"Crit. Care."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0140-6736(84)92623-0","article-title":"Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients","volume":"2","author":"Skoldenberg","year":"1984","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1136\/jnnp.63.3.321","article-title":"Herpes simplex encephalitis treated with acyclovir: Diagnosis and long term outcome","volume":"63","author":"McGrath","year":"1997","journal-title":"J. Neurol. Neurosurg. Psy."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1080\/00365540110080485","article-title":"Neurologic morbidity after herpes simplex virus type 2 meningitis: A retrospective study of 40 patients","volume":"34","author":"Aurelius","year":"2002","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0140-6736(88)90997-X","article-title":"Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome","volume":"1","author":"Corey","year":"1988","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/CMR.17.1.1-13.2004","article-title":"Neonatal herpes simplex infection","volume":"17","author":"Kimberlin","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1099\/0022-1317-71-2-405","article-title":"Neuroinvasion by herpes simplex virus. An in vitro model for characterization of neurovirulent strains","volume":"71","author":"Bergstrom","year":"1990","journal-title":"J. Gen. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1126\/science.1139522","article-title":"TLR3 deficiency in patients with herpes simplex encephalitis","volume":"317","author":"Zhang","year":"2007","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/schbul\/sbu032","article-title":"Persistent infection by HSV-1 is associated with changes in functional architecture of iPSC-derived neurons and brain activation patterns underlying working memory performance","volume":"41","author":"Prasad","year":"2015","journal-title":"Schizophr. Bull."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nature11583","article-title":"Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells","volume":"491","author":"Lafaille","year":"2012","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00111-19","DOI":"10.1128\/JVI.00111-19","article-title":"Modeling Herpes Simplex Virus 1 Infections in Human Central Nervous System Neuronal Cells Using Two- and Three-Dimensional Cultures Derived from Induced Pluripotent Stem Cells","volume":"93","author":"Bloom","year":"2019","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29200","DOI":"10.1038\/srep29200","article-title":"Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation","volume":"6","author":"Bergstrom","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41598-020-57516-7","article-title":"Accelerated neuronal and synaptic maturation by BrainPhys medium increases Abeta secretion and alters Abeta peptide ratios from iPSC-derived cortical neurons","volume":"10","author":"Satir","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nn.3041","article-title":"Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses","volume":"15","author":"Shi","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/nprot.2012.116","article-title":"Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks","volume":"7","author":"Shi","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1242\/dev.123851","article-title":"Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro","volume":"142","author":"Kirwan","year":"2015","journal-title":"Development"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.1093\/hmg\/ddv246","article-title":"Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT","volume":"24","author":"Sposito","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/01913129009050876","article-title":"Agarose embedding: A new method for the ultrastructural examination of the in-situ morphology of cell cultures","volume":"14","author":"Widehn","year":"1990","journal-title":"Ultrastruct Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3181\/00379727-118-29763","article-title":"Growth and Cytopathic Effect of Rubella Virus in a Line of Green Monkey Kidney Cells","volume":"118","author":"Guenalp","year":"1965","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1128\/JCM.43.5.2058-2064.2005","article-title":"Detection and typing of Herpes Simplex virus (HSV) in mucocutaneous samples by TaqMan PCR targeting a gB segment homologous for HSV types 1 and 2","volume":"43","author":"Namvar","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E2725","DOI":"10.1073\/pnas.1504393112","article-title":"Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro","volume":"112","author":"Bardy","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/infdis\/144.5.464","article-title":"Differences in neurovirulence among isolates of Herpes simplex virus types 1 and 2 in mice using four routes of infection","volume":"144","author":"Richards","year":"1981","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrneurol.2010.4","article-title":"Cerebrospinal fluid and plasma biomarkers in Alzheimer disease","volume":"6","author":"Blennow","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/46065","article-title":"CaMKII regulates the density of central glutamatergic synapses in vivo","volume":"402","author":"Rongo","year":"1999","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nn.2329","article-title":"betaCaMKII controls the direction of plasticity at parallel fiber-Purkinje cell synapses","volume":"12","author":"Hoebeek","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1523\/JNEUROSCI.21-14-05089.2001","article-title":"Experience-dependent gene expression in the rat hippocampus after spatial learning: A comparison of the immediate-early genes Arc, c-fos, and zif268","volume":"21","author":"Guzowski","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.tins.2011.08.007","article-title":"Arc in synaptic plasticity: From gene to behavior","volume":"34","author":"Korb","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_39","first-page":"78","article-title":"Role of Immediate-Early Genes in Synaptic Plasticity and Neuronal Ensembles Underlying the Memory Trace","volume":"8","author":"Minatohara","year":"2015","journal-title":"Front Mol. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/0042-6822(74)90390-0","article-title":"Transcription of herpes simplex type 1 DNA in nuclei isolated from infected HEp-2 and KB cells","volume":"60","author":"Alwine","year":"1974","journal-title":"Virology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1128\/jvi.21.3.996-1001.1977","article-title":"Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B","volume":"21","author":"Costanzo","year":"1977","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1099\/0022-1317-33-3-471","article-title":"The effects of herpes simplex virus type 1 on cellular DNA-dependent RNA polymerase activities","volume":"33","author":"Preston","year":"1976","journal-title":"J. Gen. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e02035","DOI":"10.1128\/JVI.02035-19","article-title":"RNA Polymerase II Promoter-Proximal Pausing and Release to Elongation Are Key Steps Regulating Herpes Simplex Virus 1 Transcription","volume":"94","author":"Birkenheuer","year":"2020","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1471-4159.2012.07825.x","article-title":"Investigating the utility of human embryonic stem cell-derived neurons to model ageing and neurodegenerative disease using whole-genome gene expression and splicing analysis","volume":"122","author":"Patani","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_45","first-page":"505","article-title":"Herpes Simplex Virus Type 1 Enhances Expression of the Synaptic Protein Arc for Its Own Benefit","volume":"12","author":"Munoz","year":"2018","journal-title":"Front Cell Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Doll, J.R., Hoebe, K., Thompson, R.L., and Sawtell, N.M. (2020). Resolution of herpes simplex virus reactivation in vivo results in neuronal destruction. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008296"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eaay8828","DOI":"10.1126\/sciadv.aay8828","article-title":"A 3 D human brain-like tissue model of herpes-induced Alzheimer\u2019s disease","volume":"6","author":"Cairns","year":"2020","journal-title":"Sci. Adv."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/2072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:14:47Z","timestamp":1760166887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/2072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["v13102072"],"URL":"https:\/\/doi.org\/10.3390\/v13102072","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]}}}