{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:00:04Z","timestamp":1785387604053,"version":"3.55.0"},"reference-count":62,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["#11241567"],"award-info":[{"award-number":["#11241567"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["#1240971"],"award-info":[{"award-number":["#1240971"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["1231851"],"award-info":[{"award-number":["1231851"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["#1241130"],"award-info":[{"award-number":["#1241130"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["ICN09_016\/ICN2021_045"],"award-info":[{"award-number":["ICN09_016\/ICN2021_045"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019783","name":"National Agency for Research and Development","doi-asserted-by":"crossref","award":["#AV25137"],"award-info":[{"award-number":["#AV25137"]}],"id":[{"id":"10.13039\/100019783","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Neurotropic viruses can alter neuronal responses in the central nervous system (CNS), significantly affecting viral clearance and disease progression. Herpes simplex virus type 1 (HSV-1) brain infection may lead to life-threatening severe acute encephalitis in untreated patients and neurological sequelae in survivors despite antiviral treatment. Notably, asymptomatic brain infection occurs in an important proportion of healthy individuals (&gt;35%) and is associated with residual chronic neuroinflammatory responses that may lead to neurodegeneration. Therefore, understanding the molecular basis of these detrimental effects and finding and advancing new therapeutic strategies to manage HSV-1 brain infections are needed. Neuropeptides are pleiotropic neuroimmune mediators expressed throughout the CNS that modulate glial activation, cytokine production, and neuronal survival. However, their regulation during HSV-1 brain infections remains largely unexplored. Here, we sought to investigate the expression dynamics of two neuropeptides, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), in two mouse strains that model human traits of symptomatic and asymptomatic HSV-1 brain infections (BALB\/c and C57BL\/6, respectively), as well as in the human neuroblastoma cell line SH-SY5Y, to uncover potential differences that could help explain the susceptibility of some individuals to develop severe HSV-1 infection. Our findings provide evidence that HSV-1 brain infection modulates NPY and VIP mRNA expression in a neurovirulence- and host-susceptibility-dependent manner, which may be associated with disease severity and chronic damage, warranting further evaluation.<\/jats:p>","DOI":"10.3390\/ijms27156735","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"6735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HSV-1 Infection Differentially Modulates NPY and VIP Neuropeptide Expression in the Mouse Brain and in Human Neuronal Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Javier","family":"Carbone-Schellman","sequence":"first","affiliation":[{"name":"Centro de Medicina Regenerativa, Facultad de Medicina, Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610717, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00e1s","family":"Sales-Salinas","sequence":"additional","affiliation":[{"name":"Centro de Medicina Regenerativa, Facultad de Medicina, Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610717, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9667-3087","authenticated-orcid":false,"given":"Rodrigo","family":"Reyes-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"},{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjam\u00edn","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Centro de Medicina Regenerativa, Facultad de Medicina, Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610717, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Pereira-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"},{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6401-5170","authenticated-orcid":false,"given":"Gisella","family":"V\u00e1squez-Canales","sequence":"additional","affiliation":[{"name":"Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Jara","sequence":"additional","affiliation":[{"name":"Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8351-3239","authenticated-orcid":false,"given":"Alfredo","family":"Molina-Berr\u00edos","sequence":"additional","affiliation":[{"name":"Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8059-3202","authenticated-orcid":false,"given":"Boris","family":"Rebolledo-Jaramillo","sequence":"additional","affiliation":[{"name":"Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610717, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis M.","family":"Kalergis","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"},{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"},{"name":"Departamento de Endocrinolog\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330023, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo A.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"},{"name":"Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330025, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-1800","authenticated-orcid":false,"given":"Luisa F.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Centro de Medicina Regenerativa, Facultad de Medicina, Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610717, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1600-0714.2007.00586.x","article-title":"Herpes Simplex Virus Type 1 Infection: Overview on Relevant Clinico-Pathological Features","volume":"37","author":"Arduino","year":"2008","journal-title":"J. Oral Pathol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Looker, K.J., Magaret, A.S., May, M.T., Turner, K.M.E., Vickerman, P., Gottlieb, S.L., and Newman, L.M. (2015). Global and Regional Estimates of Prevalent and Incident Herpes Simplex Virus Type 1 Infections in 2012. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140765"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22766","DOI":"10.3402\/jom.v5i0.22766","article-title":"Herpesviruses: Latency and Reactivation\u2014Viral Strategies and Host Response","volume":"5","author":"Grinde","year":"2013","journal-title":"J. Oral Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.ncl.2018.06.005","article-title":"Manifestations of Herpes Virus Infections in the Nervous System","volume":"36","author":"Steiner","year":"2018","journal-title":"Neurol. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3233\/JAD-131706","article-title":"Inflammatory and Neurodegeneration Markers during Asymptomatic HSV-1 Reactivation","volume":"39","author":"Martin","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s42003-024-06486-x","article-title":"Asymptomatic Herpes Simplex Virus Brain Infection Elicits Cellular Senescence Phenotypes in the Central Nervous System of Mice Suffering Multiple Sclerosis-like Disease","volume":"7","author":"Duarte","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00335-018-9772-5","article-title":"Insights into the Pathogenesis of Herpes Simplex Encephalitis from Mouse Models","volume":"29","author":"Mancini","year":"2018","journal-title":"Mamm. Genome"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10086","DOI":"10.1128\/JVI.78.18.10086-10095.2004","article-title":"Re-Evaluating Natural Resistance to Herpes Simplex Virus Type 1","volume":"78","author":"Halford","year":"2004","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1750-3639.2009.00354.x","article-title":"Chronic Cortical and Subcortical Pathology with Associated Neurological Deficits Ensuing Experimental Herpes Encephalitis","volume":"20","author":"Armien","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6417","DOI":"10.4049\/jimmunol.181.9.6417","article-title":"Prolonged Microglial Cell Activation and Lymphocyte Infiltration Following Experimental Herpes Encephalitis","volume":"181","author":"Marques","year":"2008","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2042-4280-3-4","article-title":"The Effect of Mouse Strain on Herpes Simplex Virus Type 1 (HSV-1) Infection of the Central Nervous System (CNS)","volume":"3","author":"Kastrukoff","year":"2012","journal-title":"Herpesviridae"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/infdis\/146.3.405","article-title":"The Role of Interferon in the Resistance of C57BL\/6 Mice to Various Doses of Herpes Simplex Virus Type 1","volume":"146","author":"Zawatzky","year":"1982","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-61779-310-3_1","article-title":"What Are Neuropeptides?","volume":"Volume 789","author":"Burbach","year":"2011","journal-title":"Methods in Molecular Biology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6408","DOI":"10.1523\/JNEUROSCI.2233-16.2017","article-title":"Neuroimmune\u2013Glia Interactions in the Sensory Ganglia Account for the Development of Acute Herpetic Neuralgia","volume":"37","author":"Silva","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12544","DOI":"10.1073\/pnas.95.21.12544","article-title":"Neuropeptides, by Direct Interaction with T Cells, Induce Cytokine Secretion and Break the Commitment to a Distinct T Helper Phenotype","volume":"95","author":"Levite","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/apha.12445","article-title":"The Homeostatic Role of Neuropeptide Y in Immune Function and Its Impact on Mood and Behaviour","volume":"213","author":"Farzi","year":"2015","journal-title":"Acta Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.clindermatol.2014.04.011","article-title":"The Role of Neuropeptides in the Control of Regional Immunity","volume":"32","author":"Lotti","year":"2014","journal-title":"Clin. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/296659a0","article-title":"Neuropeptide Y\u2014A Novel Brain Peptide with Structural Similarities to Peptide YY and Pancreatic Polypeptide","volume":"296","author":"Tatemoto","year":"1982","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1021\/acsptsci.4c00666","article-title":"Characterization of [3H]Propionylated Human Peptide YY-A New Probe for Neuropeptide Y Y2 Receptor Binding Studies","volume":"8","author":"Schettler","year":"2025","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.1523\/JNEUROSCI.20-10-03622.2000","article-title":"Vasoactive Intestinal Peptide and Pituitary Adenylyl Cyclase-Activating Polypeptide Inhibit Tumor Necrosis Factor-\u03b1 Production in Injured Spinal Cord and in Activated Microglia via a CAMP-Dependent Pathway","volume":"20","author":"Kim","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1189\/jlb.0702372","article-title":"Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Inhibit the Production of Inflammatory Mediators by Activated Microglia","volume":"73","author":"Delgado","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1172\/JCI116527","article-title":"Replication, Establishment of Latency, and Induced Reactivation of Herpes Simplex Virus \u03931 34.5 Deletion Mutants in Rodent Models","volume":"91","author":"Whitley","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_23","first-page":"73","article-title":"Role of Virus-Induced Neuropeptides in the Brain in the Pathogenesis of Rabies","volume":"131","author":"Weihe","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11076","DOI":"10.1128\/JVI.01022-10","article-title":"Neuropeptide Y Has a Protective Role during Murine Retrovirus-Induced Neurological Disease","volume":"84","author":"Du","year":"2010","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/apha.12427","article-title":"The Neuropeptide Vasoactive Intestinal Peptide: Direct Effects on Immune Cells and Involvement in Inflammatory and Autoimmune Diseases","volume":"213","author":"Ganea","year":"2015","journal-title":"Acta Physiol."},{"key":"ref_26","first-page":"65","article-title":"A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases","volume":"21","author":"Juarranz","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, J.M., Darlak, K.A., Southerland, L., Hossain, M.S., Jaye, D.L., Josephson, C.D., Rosenthal, H., and Waller, E.K. (2013). VIPhyb, an Antagonist of Vasoactive Intestinal Peptide Receptor, Enhances Cellular Antiviral Immunity in Murine Cytomegalovirus Infected Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063381"},{"key":"ref_28","first-page":"419","article-title":"Vasoactive Intestinal Peptide: A Potential Target for Antiviral Therapy","volume":"74","author":"He","year":"2022","journal-title":"Acta Physiol. Sin."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21171","DOI":"10.1038\/s41598-021-00391-7","article-title":"The C-Rel Transcription Factor Limits Early Interferon and Neuroinflammatory Responses to Prevent Herpes Simplex Encephalitis Onset in Mice","volume":"11","author":"Mancini","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s13311-016-0433-7","article-title":"Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management","volume":"13","author":"Bradshaw","year":"2016","journal-title":"Neurotherapeutics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"89934","DOI":"10.5501\/wjv.v13.i1.89934","article-title":"Herpes Simplex Keratitis: A Brief Clinical Overview","volume":"13","author":"Musa","year":"2024","journal-title":"World J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1080\/21505594.2021.1982373","article-title":"Pathogenesis and Virulence of Herpes Simplex Virus","volume":"12","author":"Zhu","year":"2021","journal-title":"Virulence"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1167\/iovs.08-3211","article-title":"Optic Neuritis in Different Strains of Mice by a Recombinant Hsv-1 Expressing Murine Interleukin-2","volume":"50","author":"Zandian","year":"2009","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.virol.2010.02.013","article-title":"Redundancy in the Immune System Restricts the Spread of HSV-1 in the Central Nervous System (CNS) of C57BL\/6 Mice","volume":"400","author":"Kastrukoff","year":"2010","journal-title":"Virology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.expneurol.2004.12.004","article-title":"CD8+-Dependent CNS Demyelination Following Ocular Infection of Mice with a Recombinant HSV-1 Expressing Murine IL-2","volume":"193","author":"Osorio","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1167\/iovs.10-6536","article-title":"Macrophage IL-12p70 Signaling Prevents HSV-1-Induced CNS Autoimmunity Triggered by Autoaggressive CD4+ Tregs","volume":"52","author":"Mott","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wilcox, D.R., and Longnecker, R. (2016). The Herpes Simplex Virus Neurovirulence Factor \u039334.5: Revealing Virus\u2013Host Interactions. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005449"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.chom.2006.12.001","article-title":"HSV-1 ICP34.5 Confers Neurovirulence by Targeting the Beclin 1 Autophagy Protein","volume":"1","author":"Orvedahl","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5048616","DOI":"10.1155\/2017\/5048616","article-title":"Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases","volume":"2017","author":"Carniglia","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31427","DOI":"10.1074\/jbc.273.47.31427","article-title":"Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Inhibit Tumor Necrosis Factor \u03b1 Transcriptional Activation by Regulating Nuclear Factor-KB and CAMP Response Element-Binding Protein\/c-Jun","volume":"273","author":"Delgado","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"41921","DOI":"10.1074\/jbc.M110.164020","article-title":"Neuropeptide y Modulation of Interleukin-1\u03b2 (IL-1\u03b2)-Induced Nitric Oxide Production in Microglia","volume":"285","author":"Ferreira","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_42","first-page":"1","article-title":"Vasoactive Intestinal Peptide Prevents Activated Microglia-induced Neurodegeneration under Inflammatory Conditions: Potential Therapeutic Role in Brain Trauma","volume":"17","author":"Delgado","year":"2003","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Duarte, L.F., Far\u00edas, M.A., \u00c1lvarez, D.M., Bueno, S.M., Riedel, C.A., and Gonz\u00e1lez, P.A. (2019). Herpes Simplex Virus Type 1 Infection of the Central Nervous System: Insights into Proposed Interrelationships with Neurodegenerative Disorders. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00046"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105084","DOI":"10.1016\/j.micinf.2022.105084","article-title":"Is There a Role for Herpes Simplex Virus Type 1 in Multiple Sclerosis?","volume":"25","author":"Duarte","year":"2023","journal-title":"Microbes Infect."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Duarte, L.F., Altamirano-Lagos, M.J., Tabares-Guevara, J.H., Opazo, M.C., D\u00edaz, M., Navarrete, R., Muza, C., Vallejos, O.P., Riedel, C.A., and Bueno, S.M. (2021). Asymptomatic Herpes Simplex Virus Type 1 Infection Causes an Earlier Onset and More Severe Experimental Autoimmune Encephalomyelitis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.635257"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1128\/JVI.02934-15","article-title":"Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection","volume":"90","author":"Woods","year":"2016","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Temerozo, J.R., de Azevedo, S.S.D., Insuela, D.B.R., Vieira, R.C., Ferreira, P.L.C., Carvalho, V.F., Bello, G., and Bou-Habib, D.C. (2018). The Neuropeptides Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Control HIV-1 Infection in Macrophages through Activation of Protein Kinases A and C. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01336"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mehboob, R., Oehme, P., Anwar, T., and von Kries, J.P. (2024). Substance P\u2014A Regulatory Peptide with Defense and Repair Functions. Results and Perspectives for the Fight against COVID-19. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1370454"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/JLB.5COVA1121-626R","article-title":"VIP Plasma Levels Associate with Survival in Severe COVID-19 Patients, Correlating with Protective Effects in SARS-CoV-2-Infected Cells","volume":"111","author":"Temerozo","year":"2022","journal-title":"J. Leukoc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.4049\/jimmunol.1100686","article-title":"Absence of Vasoactive Intestinal Peptide Expression in Hematopoietic Cells Enhances Th1 Polarization and Antiviral Immunity in Mice","volume":"187","author":"Li","year":"2011","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0006-8993(99)01644-3","article-title":"VIP and D-Ala-Peptide T-Amide Release Chemokines Which Prevent HIV-1 GP120-Induced Neuronal Death","volume":"838","author":"Brenneman","year":"1999","journal-title":"Brain Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/head.13084","article-title":"Overview of Neuropeptides: Awakening the Senses?","volume":"57","author":"Russo","year":"2017","journal-title":"Headache"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1007\/s00431-023-05417-y","article-title":"Plasma Levels of Neurogenic Inflammation Related Neuropeptides in Pediatric Patients with Community-Acquired Pneumonia and Their Potential Diagnostic Value in Distinguishing Viral and Bacterial Pneumonia","volume":"183","author":"Bekdas","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/0022-510X(95)00305-L","article-title":"Increased Neuropeptide Y-like Immunoreactivity in Cerebrospinal Fluid and Plasma of Human Immunodeficiency Virus-Infected Patients: Relationship to HIV Encephalopathy","volume":"136","author":"Malessa","year":"1996","journal-title":"J. Neurol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/glia.10098","article-title":"Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Inhibit Chemokine Production in Activated Microglia","volume":"39","author":"Delgado","year":"2002","journal-title":"Glia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1471-4159.2011.07541.x","article-title":"Neuropeptide y Inhibits Interleukin-1 Beta-Induced Microglia Motility","volume":"120","author":"Ferreira","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ambrosio, A., Elvas, F., Madeira, M., Brudzewsky, D., Martins, J., Martins, T., Cavadas, C., and Santiago, A. (2013). Neuropeptide Y Y1 Receptor Is Neuroprotective and Modulates Microglia Reactivity in the Rat Retina. Acta Ophthalmol., 91.","DOI":"10.1111\/j.1755-3768.2013.1742.x"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1749-6632.2000.tb06954.x","article-title":"Receptors and Transcriptional Factors Involved in the Anti-Inflammatory Activity of VIP and PACAP","volume":"921","author":"Leceta","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Temerozo, J.R., Joaquim, R., Regis, E.G., Savino, W., and Bou-Habib, D.C. (2013). Macrophage Resistance to HIV-1 Infection Is Enhanced by the Neuropeptides VIP and PACAP. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067701"},{"key":"ref_60","unstructured":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011). Care and Use of Laboratory Animals, National Academies Press. [8th ed.]."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/1742-2094-8-169","article-title":"Neuropeptide Y Inhibits Interleukin-1\u03b2-Induced Phagocytosis by Microglial Cells","volume":"8","author":"Ferreira","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Palanivel, V., Gupta, V., Mirshahvaladi, S.S.O., Sharma, S., Gupta, V., Chitranshi, N., Mirzaei, M., Graham, S.L., and Basavarajappa, D. (2022). Neuroprotective Effects of Neuropeptide Y on Human Neuroblastoma SH-SY5Y Cells in Glutamate Excitotoxicity and ER Stress Conditions. Cells, 11.","DOI":"10.3390\/cells11223665"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6735\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:30:01Z","timestamp":1785385801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6735"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":62,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156735"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156735","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}