{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:33Z","timestamp":1785428073376,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["466759708"],"award-info":[{"award-number":["466759708"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"award":["466759708"],"award-info":[{"award-number":["466759708"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Alphaherpesviruses, including Herpes Simplex Virus 1 (HSV-1) and Pseudorabies Virus (PrV), establish lifelong latency in the nervous system and can cause recurrent disease. While latency has classically been attributed to peripheral sensory ganglia, accumulating evidence indicates that the central nervous system (CNS) may also serve as a site of long-term viral persistence and reactivation. Here, we investigated the CNS as a viral reservoir using the attenuated mutant PrV-\u2206UL21\/US3\u2206kin, which preferentially targets mesiotemporal brain regions. Following intranasal inoculation, mice were analyzed at 11\u201314, 21, 28, 42, 105, and 190 days post-infection (dpi). To assess the reactivation potential, a subset of animals received cyclophosphamide\/dexamethasone at 170 dpi. Viral transcripts were detected by RNAscope\u2122 in situ hybridization and RT-qPCR targeting the lytic gene UL19 encoding the major capsid protein and the latency-associated transcript (LAT). Histopathology included hematoxylin and eosin staining and immunohistochemistry for CD3, Iba1, GFAP, cleaved caspase-3 and viral glycoprotein gB. UL19 RNA signals displayed marked regional and temporal heterogeneity, with prominent detection in mesiotemporal structures. In contrast, LAT RNA levels remained low overall, with a transient peak during the acute phase. RT-qPCR confirmed high UL19 and LAT transcript levels during early infection, while LAT transcription returned to baseline levels thereafter. Histopathology showed a transition from acute necrotizing meningoencephalitis to prolonged low-grade inflammation with glial activation and focal apoptosis. Notably, UL19 RNA signals strongly correlated with T-cell infiltration, particularly at 42 dpi. Together, these findings define regional and temporal patterns of long-term PrV transcriptional activity and associated neuropathology in the murine CNS.<\/jats:p>","DOI":"10.3390\/pathogens15040395","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:09:00Z","timestamp":1775549340000},"page":"395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regional and Temporal Patterns of Long-Term Pseudorabies Virus Detection and Neuropathology in the Murine CNS"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1058-4842","authenticated-orcid":false,"given":"Viktoria","family":"Korff","sequence":"first","affiliation":[{"name":"Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7033-955X","authenticated-orcid":false,"given":"Issam","family":"El-Debs","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara G.","family":"Klupp","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-398X","authenticated-orcid":false,"given":"Conrad M.","family":"Freuling","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-4970","authenticated-orcid":false,"given":"Jens P.","family":"Teifke","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Mettenleiter","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Sehl-Ewert","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.2217\/fvl-2018-0023","article-title":"Latent versus productive infection: The alpha herpesvirus switch","volume":"13","author":"Koyuncu","year":"2018","journal-title":"Future Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.2000.0529","article-title":"Three classes of cell surface receptors for alphaherpesvirus entry","volume":"275","author":"Spear","year":"2000","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0168-1702(02)00352-0","article-title":"Pathogenesis of neurotropic herpesviruses: Role of viral glycoproteins in neuroinvasion and transneuronal spread","volume":"92","author":"Mettenleiter","year":"2003","journal-title":"Virus Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev-micro-092611-150051","article-title":"Herpesvirus transport to the nervous system and back again","volume":"66","author":"Smith","year":"2012","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1023\/A:1012517221937","article-title":"Gene Expression Analyzed by Microarrays in HSV-1 Latent Mouse Trigeminal Ganglion Following Heat Stress","volume":"23","author":"Hill","year":"2001","journal-title":"Virus Genes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1099\/0022-1317-28-3-341","article-title":"Acute and Recurrent Infection with Herpes Simplex Virus in the Mouse: A Model for Studying Latency and Recurrent Disease","volume":"28","author":"Hill","year":"1975","journal-title":"J. Gen. Virol."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.2460\/ajvr.1980.41.08.1315","article-title":"Isolation of pseudorabies virus from trigeminal ganglia of a latently infected sow","volume":"41","author":"Gutekunst","year":"1980","journal-title":"Am. J. Vet. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Roizman, B. (1985). Molecular Biology of Pseudorabies Virus. The Herpesviruses: Volume 3, Springer.","DOI":"10.1007\/978-1-4613-2383-9"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1128\/MMBR.69.3.462-500.2005","article-title":"Molecular biology of pseudorabies virus: Impact on neurovirology and veterinary medicine","volume":"69","author":"Pomeranz","year":"2005","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1128\/JVI.02181-14","article-title":"A 2.5-kilobase deletion containing a cluster of nine microRNAs in the latency-associated-transcript locus of the pseudorabies virus affects the host response of porcine trigeminal ganglia during established latency","volume":"89","author":"Mahjoub","year":"2015","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Anselmo, A., Flori, L., Jaffrezic, F., Rutigliano, T., Cecere, M., Cortes-Perez, N., Lef\u00e8vre, F., Rogel-Gaillard, C., and Giuffra, E. (2011). Co-Expression of Host and Viral MicroRNAs in Porcine Dendritic Cells Infected by the Pseudorabies Virus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017374"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1126\/science.287.5457.1500","article-title":"Virus-Induced Neuronal Apoptosis Blocked by the Herpes Simplex Virus Latency-Associated Transcript","volume":"287","author":"Perng","year":"2000","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/nature07103","article-title":"MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs","volume":"454","author":"Umbach","year":"2008","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9131","DOI":"10.1128\/JVI.00871-09","article-title":"Two small RNAs encoded within the first 1.5 kilobases of the herpes simplex virus type 1 latency-associated transcript can inhibit productive infection and cooperate to inhibit apoptosis","volume":"83","author":"Shen","year":"2009","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1385\/IR:36:1:119","article-title":"A Triple Entente: Virus, Neurons, and CD8+ T Cells Maintain HSV-1 Latency","volume":"36","author":"Divito","year":"2006","journal-title":"Immunol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"109017","DOI":"10.1016\/j.exer.2022.109017","article-title":"Regulation of herpes simplex virus type 1 latency-reactivation cycle and ocular disease by cellular signaling pathways","volume":"218","author":"Harrison","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1172\/JCI136225","article-title":"Herpesvirus latency","volume":"130","author":"Cohen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11264","DOI":"10.1128\/JVI.01616-14","article-title":"In vivo reactivation of latent herpes simplex virus 1 in mice can occur in the brain before occurring in the trigeminal ganglion","volume":"88","author":"Yao","year":"2014","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e0108122","DOI":"10.1128\/jvi.01081-22","article-title":"Herpes Simplex Virus Type 1 Preferentially Enhances Neuro-Inflammation and Senescence in Brainstem of Female Mice","volume":"96","author":"Sivasubramanian","year":"2022","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.tim.2020.03.003","article-title":"Herpes Simplex Virus-1 in the Brain: The Dark Side of a Sneaky Infection","volume":"28","author":"Marcocci","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/QCO.0000000000000554","article-title":"Herpes simplex virus encephalitis update","volume":"32","author":"Stahl","year":"2019","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","unstructured":"Feng, S., Liu, Y., Zhou, Y., Shu, Z., Cheng, Z., Brenner, C., and Feng, P. (2023). Mechanistic insights into the role of herpes simplex virus 1 in Alzheimer\u2019s disease. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1245904"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102200","DOI":"10.1016\/j.coph.2022.102200","article-title":"Role of HSV-1 in Alzheimer\u2019s disease pathogenesis: A challenge for novel preventive\/therapeutic strategies","volume":"63","author":"Protto","year":"2022","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_26","first-page":"99","article-title":"Aujeszky\u2019s disease (pseudorabies) virus: The virus and molecular pathogenesis\u2014State of the art, June 1999","volume":"31","author":"Mettenleiter","year":"2000","journal-title":"Vet. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1006\/viro.1994.1576","article-title":"Propagation of Pseudorabies Virus in the Nervous System of the Mouse after Intranasal Inoculation","volume":"204","author":"Babic","year":"1994","journal-title":"Virology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sehl, J., H\u00f6lper, J.E., Klupp, B.G., Baumbach, C., Teifke, J.P., and Mettenleiter, T.C. (2020). An improved animal model for herpesvirus encephalitis in humans. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008445"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e13031","DOI":"10.1111\/bpa.13031","article-title":"Clinical, neuropathological, and immunological short- and long-term feature of a mouse model mimicking human herpes virus encephalitis","volume":"32","author":"Schwaiger","year":"2022","journal-title":"Brain Pathol."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1055\/s-2007-973546","article-title":"Chronic active destructive herpes simplex encephalitis with recovery of viral DNA 12 years after disease onset","volume":"29","author":"Asenbauer","year":"1998","journal-title":"Neuropediatrics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S1474-4422(18)30244-8","article-title":"Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: A prospective observational study and retrospective analysis","volume":"17","author":"Armangue","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0882-4010(92)90064-U","article-title":"A murine model of pseudorabies virus latency","volume":"12","author":"Osorio","year":"1992","journal-title":"Microb. Pathog."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/0042-6822(59)90068-6","article-title":"A Comparison of Herpes Simplex and Pseudorabies Viruses","volume":"7","author":"Kaplan","year":"1959","journal-title":"Virology"},{"key":"ref_35","first-page":"e3564","article-title":"Whole animal perfusion fixation for rodents","volume":"65","author":"Gage","year":"2012","journal-title":"J. Vis. Exp."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1177\/0192623311401044","article-title":"Histopathological evaluation of the nervous system in National Toxicology Program rodent studies: A modified approach","volume":"39","author":"Rao","year":"2011","journal-title":"Toxicol. Pathol."},{"key":"ref_37","unstructured":"Paxinos, G., and Franklin, K.B.J. (2001). The Mouse Brain in Stereotaxic Coordinates, Academic Press. [2nd ed.]."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: A novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"Wang","year":"2012","journal-title":"J. Mol. Diagn."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jviromet.2014.08.022","article-title":"Molecular double-check strategy for the identification and characterization of Suid herpesvirus 1","volume":"209","author":"Wernike","year":"2014","journal-title":"J. Virol. Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e0096824","DOI":"10.1128\/jvi.00968-24","article-title":"Olfactory and trigeminal routes of HSV-1 CNS infection with regional microglial heterogeneity","volume":"98","author":"Niemeyer","year":"2024","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0022-510X(87)90233-4","article-title":"Contrasting patterns of virus spread and neuropathology following microinjection of herpes simplex virus into the hippocampus or cerebellum of mice","volume":"79","author":"McFarland","year":"1987","journal-title":"J. Neurol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1111\/j.1460-9568.2003.03075.x","article-title":"Herpes simplex virus type 1 inoculation enhances hippocampal excitability and seizure susceptibility in mice","volume":"18","author":"Wu","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chee, K., Razmara, A., Geller, A.S., Harris, W.B., Restrepo, D., Thompson, J.A., and Kramer, D.R. (2022). The role of the piriform cortex in temporal lobe epilepsy: A current literature review. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.1042887"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Costa, B., and Vale, N. (2024). Virus-Induced Epilepsy vs. Epilepsy Patients Acquiring Viral Infection: Unravelling the Complex Relationship for Precision Treatment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073730"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00705-021-04959-6","article-title":"Viral infections and their relationship to neurological disorders","volume":"166","author":"Wouk","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1007\/s13365-011-0063-0","article-title":"Control of HSV-1 latency in human trigeminal ganglia--current overview","volume":"17","author":"Held","year":"2011","journal-title":"J. Neurovirol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1126\/science.280.5369.1618","article-title":"Entry of Alphaherpesviruses Mediated by Poliovirus Receptor-Related Protein 1 and Poliovirus Receptor","volume":"280","author":"Geraghty","year":"1998","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s13365-016-0504-x","article-title":"Distribution of cellular HSV-1 receptor expression in human brain","volume":"23","author":"Lathe","year":"2017","journal-title":"J. Neurovirol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/13550280600760594","article-title":"Spatiotemporal changes of the herpes simplex virus entry receptor nectin-1 in murine brain during postnatal development","volume":"12","author":"Prandovszky","year":"2006","journal-title":"J. Neurovirol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.neuroscience.2025.08.024","article-title":"Neurotropism of alphaherpesviruses is most prominent in the mesiotemporal, piriform and prefrontal cortices in mice","volume":"584","author":"Korff","year":"2025","journal-title":"Neuroscience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nm.3108","article-title":"Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses","volume":"19","author":"Cho","year":"2013","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.coi.2021.07.004","article-title":"Neuron-intrinsic immunity to viruses in mice and humans","volume":"72","author":"Zhang","year":"2021","journal-title":"Curr. Opin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17590914211053505","DOI":"10.1177\/17590914211053505","article-title":"Simultaneous Detection of Herpes Simplex Virus Type 1 Latent and Lytic Transcripts in Brain Tissue","volume":"14","author":"Zhang","year":"2022","journal-title":"ASN Neuro"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1128\/jvi.69.3.1389-1399.1995","article-title":"Quantification of transcripts from the ICP4 and thymidine kinase genes in mouse ganglia latently infected with herpes simplex virus","volume":"69","author":"Kramer","year":"1995","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1073\/pnas.022301899","article-title":"Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice","volume":"99","author":"Feldman","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1084\/jem.191.9.1459","article-title":"CD8(+) T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons","volume":"191","author":"Liu","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1128\/JVI.77.7.4127-4138.2003","article-title":"Quantitative analysis of herpes simplex virus reactivation in vivo demonstrates that reactivation in the nervous system is not inhibited at early times postinoculation","volume":"77","author":"Sawtell","year":"2003","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.4049\/jimmunol.1600207","article-title":"Resident T Cells Are Unable to Control Herpes Simplex Virus-1 Activity in the Brain Ependymal Region during Latency","volume":"197","author":"Menendez","year":"2016","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5343","DOI":"10.1128\/JVI.72.7.5343-5350.1998","article-title":"The latent herpes simplex virus type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation","volume":"72","author":"Sawtell","year":"1998","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6888","DOI":"10.1128\/JVI.72.8.6888-6892.1998","article-title":"The probability of in vivo reactivation of herpes simplex virus type 1 increases with the number of latently infected neurons in the ganglia","volume":"72","author":"Sawtell","year":"1998","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ma, J.Z., Russell, T.A., Spelman, T., Carbone, F.R., and Tscharke, D.C. (2014). Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004237"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1128\/JVI.01791-10","article-title":"The herpes simplex virus type 1 latency-associated transcript can protect neuron-derived C1300 and Neuro2A cells from granzyme B-induced apoptosis and CD8 T-cell killing","volume":"85","author":"Jiang","year":"2011","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.1128\/JVI.02589-05","article-title":"Influence of pseudorabies virus proteins on neuroinvasion and neurovirulence in mice","volume":"80","author":"Klopfleisch","year":"2006","journal-title":"J. Virol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/4\/395\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:18:49Z","timestamp":1775722729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/4\/395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":63,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["pathogens15040395"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15040395","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]}}}