{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T08:44:17Z","timestamp":1779353057184,"version":"3.51.4"},"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS064022"],"award-info":[{"award-number":["R01 NS064022"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE026749"],"award-info":[{"award-number":["R01 DE026749"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 EY017272"],"award-info":[{"award-number":["T32 EY017272"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014147","name":"Charles E. Kaufman Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014147","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 EY08098"],"award-info":[{"award-number":["P30 EY08098"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001607","name":"Eye and Ear Foundation of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Herpes zoster, the result of varicella-zoster virus (VZV) reactivation, is frequently complicated by difficult-to-treat chronic pain states termed postherpetic neuralgia (PHN). While there are no animal models of VZV-induced pain following viral reactivation, subcutaneous VZV inoculation of the rat causes long-term nocifensive behaviors indicative of mechanical and thermal hypersensitivity. Previous studies using UV-inactivated VZV in the rat model suggest viral gene expression is required for the development of pain behaviors. However, it remains unclear if complete infection processes are needed for VZV to induce hypersensitivity in this host. To further assess how gene expression and replication contribute, we developed and characterized three replication-conditional VZV using a protein degron system to achieve drug-dependent stability of essential viral proteins. Each virus was then assessed for induction of hypersensitivity in rats under replication permissive and nonpermissive conditions. VZV with a degron fused to ORF9p, a late structural protein that is required for virion assembly, induced nocifensive behaviors under both replication permissive and nonpermissive conditions, indicating that complete VZV replication is dispensable for the induction of hypersensitivity. This conclusion was confirmed by showing that a genetic deletion recombinant VZV lacking DNA packaging protein ORF54p still induced prolonged hypersensitivities in the rat. In contrast, VZV with a degron fused to the essential IE4 or IE63 proteins, which are involved in early gene regulation of expression, induced nocifensive behaviors only under replication permissive conditions, indicating importance of early gene expression events for induction of hypersensitivity. These data establish that while early viral gene expression is required for the development of nocifensive behaviors in the rat, complete replication is dispensable. We postulate this model reflects events leading to clinical PHN, in which a population of ganglionic neurons become abortively infected with VZV during reactivation and survive, but host signaling becomes altered in order to transmit ongoing pain.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009689","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T17:25:31Z","timestamp":1625592331000},"page":"e1009689","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Varicella-zoster virus early infection but not complete replication is required for the induction of chronic hypersensitivity in rat models of postherpetic neuralgia"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1550-1516","authenticated-orcid":true,"given":"Benjamin E.","family":"Warner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-7757","authenticated-orcid":true,"given":"Michael B.","family":"Yee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingdi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-8144","authenticated-orcid":true,"given":"Rebecca S.","family":"Hornung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-2695","authenticated-orcid":true,"given":"Benedikt B.","family":"Kaufer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7570-8922","authenticated-orcid":true,"given":"Robert J.","family":"Visalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0117-542X","authenticated-orcid":true,"given":"Phillip R.","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William F.","family":"Goins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R.","family":"Kinchington","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"issue":"3","key":"ppat.1009689.ref001","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrmicro3215","article-title":"Molecular mechanisms of varicella zoster virus pathogenesis","volume":"12","author":"L Zerboni","year":"2014","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"ppat.1009689.ref002","doi-asserted-by":"crossref","first-page":"15039","DOI":"10.1038\/s41598-017-15390-w","article-title":"Decreased absolute numbers of CD3+ T cells and CD8+ T cells during aging in herpes zoster patients","volume":"7","author":"L Wei","year":"2017","journal-title":"Sci Rep"},{"issue":"22","key":"ppat.1009689.ref003","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1056\/NEJMoa051016","article-title":"A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults","volume":"352","author":"MN Oxman","year":"2005","journal-title":"N Engl J Med"},{"issue":"RR-4","key":"ppat.1009689.ref004","first-page":"1","article-title":"Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP)","volume":"56","author":"Advisory Committee on Immunization Practices C for DC and P (CDC)","year":"2007","journal-title":"MMWR Recomm reports Morb Mortal Wkly report Recomm reports"},{"issue":"22","key":"ppat.1009689.ref005","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1056\/NEJMoa1501184","article-title":"Efficacy of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults","volume":"372","author":"H Lal","year":"2015","journal-title":"N Engl J Med"},{"issue":"3","key":"ppat.1009689.ref006","doi-asserted-by":"crossref","first-page":"103","DOI":"10.15585\/mmwr.mm6703a5","article-title":"Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines","volume":"67","author":"KL Dooling","year":"2018","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"370","key":"ppat.1009689.ref007","first-page":"1","article-title":"Shingles Vaccination Among Adults Aged 60 and Over: United States, 2018","author":"EP Terlizzi","year":"2020","journal-title":"NCHS Data Brief"},{"issue":"6","key":"ppat.1009689.ref008","doi-asserted-by":"crossref","first-page":"e004833","DOI":"10.1136\/bmjopen-2014-004833","article-title":"Systematic review of incidence and complications of herpes zoster: towards a global perspective","volume":"4","author":"K Kawai","year":"2014","journal-title":"BMJ Open"},{"issue":"19","key":"ppat.1009689.ref009","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1016\/j.vaccine.2018.03.053","article-title":"The public health value of vaccination for seniors in Europe","volume":"36","author":"S Esposito","year":"2018","journal-title":"Vaccine"},{"issue":"12","key":"ppat.1009689.ref010","doi-asserted-by":"crossref","first-page":"991","DOI":"10.2165\/0002512-200825120-00002","article-title":"Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient","volume":"25","author":"RW Johnson","year":"2008","journal-title":"Drugs Aging"},{"issue":"1","key":"ppat.1009689.ref011","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/j.pain.0000000000000307","article-title":"A systematic review and meta-analysis of risk factors for postherpetic neuralgia","volume":"157","author":"HJ Forbes","year":"2016","journal-title":"Pain"},{"issue":"SUPPL 1","key":"ppat.1009689.ref012","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1016\/S1386-6532(10)70003-2","article-title":"The impact of varicella zoster virus: chronic pain","volume":"48 Suppl 1","author":"W Opstelten","year":"2010","journal-title":"J Clin Virol"},{"issue":"1\u20132","key":"ppat.1009689.ref013","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0304-3959(00)00481-4","article-title":"The density of remaining nerve endings in human skin with and without postherpetic neuralgia after shingles","volume":"92","author":"AL Oaklander","year":"2001","journal-title":"Pain"},{"issue":"3","key":"ppat.1009689.ref014","first-page":"373","article-title":"Treatment of herpes zoster","volume":"54","author":"W Opstelten","year":"2008","journal-title":"Can Fam Physician"},{"issue":"2","key":"ppat.1009689.ref015","doi-asserted-by":"crossref","first-page":"89","DOI":"10.7326\/0003-4819-123-2-199507150-00002","article-title":"Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group","volume":"123","author":"S Tyring","year":"1995","journal-title":"Ann Intern Med"},{"issue":"10","key":"ppat.1009689.ref016","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1128\/AAC.45.10.2771-2774.2001","article-title":"Acyclovir for treatment of postherpetic neuralgia: efficacy and pharmacokinetics","volume":"45","author":"EP Acosta","year":"2001","journal-title":"Antimicrob Agents Chemother"},{"issue":"12","key":"ppat.1009689.ref017","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1128\/JVI.02793-06","article-title":"Productive varicella-zoster virus infection of cultured intact human ganglia","volume":"81","author":"K Gowrishankar","year":"2007","journal-title":"J Virol"},{"issue":"2","key":"ppat.1009689.ref018","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/00002508-199906000-00003","article-title":"Pain and somatosensory dysfunction in acute herpes zoster","volume":"15","author":"M Haanp\u00e4\u00e4","year":"1999","journal-title":"Clin J Pain"},{"issue":"1","key":"ppat.1009689.ref019","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0885-3924(00)00149-4","article-title":"Allodynia and pinprick hypesthesia in acute herpes zoster, and the development of postherpetic neuralgia","volume":"20","author":"M Haanp\u00e4\u00e4","year":"2000","journal-title":"J Pain Symptom Manage"},{"issue":"5","key":"ppat.1009689.ref020","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1128\/JVI.03445-13","article-title":"Analysis of T cell responses during active varicella-zoster virus reactivation in human ganglia","volume":"88","author":"M Steain","year":"2014","journal-title":"J Virol"},{"issue":"17","key":"ppat.1009689.ref021","doi-asserted-by":"crossref","first-page":"8861","DOI":"10.1128\/JVI.01020-10","article-title":"Characterization of the host immune response in human Ganglia after herpes zoster","volume":"84","author":"K Gowrishankar","year":"2010","journal-title":"J Virol"},{"issue":"4","key":"ppat.1009689.ref022","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.nurt.2009.07.005","article-title":"Postherpetic neuralgia: from preclinical models to the clinic","volume":"6","author":"A Delaney","year":"2009","journal-title":"Neurotherapeutics"},{"issue":"1","key":"ppat.1009689.ref023","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/jnr.490260110","article-title":"An in vivo model of varicella-zoster virus latent infection of dorsal root ganglia","volume":"26","author":"C Sadzot-Delvaux","year":"1990","journal-title":"J Neurosci Res"},{"issue":"5 SUPPL","key":"ppat.1009689.ref024","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1086\/514261","article-title":"Evidence of latent varicella-zoster virus in rat dorsal root ganglia","volume":"178 Suppl","author":"P Annunziato","year":"1998","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1009689.ref025","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1006\/viro.2001.1173","article-title":"Varicella-Zoster virus gene expression in latently infected rat dorsal root ganglia","volume":"289","author":"PGE Kennedy","year":"2001","journal-title":"Virology"},{"issue":"Pt 9","key":"ppat.1009689.ref026","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1099\/0022-1317-80-9-2433","article-title":"Behavioural changes in the rat following infection with varicella-zoster virus","volume":"80","author":"SM Fleetwood-Walker","year":"1999","journal-title":"J Gen Virol"},{"issue":"2","key":"ppat.1009689.ref027","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.brainresrev.2004.07.008","article-title":"Allodynia in rats infected with varicella zoster virus\u2014a small animal model for post-herpetic neuralgia","volume":"46","author":"RG Dalziel","year":"2004","journal-title":"Brain Res Brain Res Rev"},{"issue":"1\u20132","key":"ppat.1009689.ref028","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.pain.2005.08.003","article-title":"Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs","volume":"118","author":"EM Garry","year":"2005","journal-title":"Pain"},{"issue":"4","key":"ppat.1009689.ref029","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.neuroscience.2006.11.029","article-title":"Further characterization of a rat model of varicella zoster virus-associated pain: Relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs","volume":"144","author":"FS Hasnie","year":"2007","journal-title":"Neuroscience"},{"issue":"6","key":"ppat.1009689.ref030","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1007\/s13365-011-0069-7","article-title":"Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models","volume":"17","author":"PR Kinchington","year":"2011","journal-title":"J Neurovirol"},{"issue":"7","key":"ppat.1009689.ref031","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/gt.2014.43","article-title":"Relief of pain induced by varicella-zoster virus in a rat model of post-herpetic neuralgia using a herpes simplex virus vector expressing enkephalin","volume":"21","author":"J-MG Guedon","year":"2014","journal-title":"Gene Ther"},{"key":"ppat.1009689.ref032","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.virol.2015.03.046","article-title":"Neuronal changes induced by Varicella Zoster Virus in a rat model of postherpetic neuralgia","volume":"482","author":"J-MG Guedon","year":"2015","journal-title":"Virology"},{"issue":"October","key":"ppat.1009689.ref033","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fnint.2017.00027","article-title":"Role for the Ventral Posterior Medial\/Posterior Lateral Thalamus and Anterior Cingulate Cortex in Affective\/Motivation Pain Induced by Varicella Zoster Virus","volume":"11","author":"PR Kramer","year":"2017","journal-title":"Front Integr Neurosci"},{"issue":"1","key":"ppat.1009689.ref034","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12883-017-0882-6","article-title":"Sex differences underlying orofacial varicella zoster associated pain in rats","volume":"17","author":"C Stinson","year":"2017","journal-title":"BMC Neurol"},{"issue":"October","key":"ppat.1009689.ref035","first-page":"1","article-title":"Aromatase derived estradiol within the thalamus modulates pain induced by varicella zoster virus","volume":"12","author":"P Kramer","year":"2018","journal-title":"Front Integr Neurosci"},{"key":"ppat.1009689.ref036","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.neuroscience.2019.06.029","article-title":"Estradiol Acts in Lateral Thalamic Region to Attenuate Varicella Zoster Virus Associated Affective Pain","volume":"414","author":"C Stinson","year":"2019","journal-title":"Neuroscience"},{"issue":"16","key":"ppat.1009689.ref037","doi-asserted-by":"crossref","first-page":"5749","DOI":"10.3390\/ijms21165749","article-title":"Comparing Gene Expression in the Parabrachial and Amygdala of Diestrus and Proestrus Female Rats after Orofacial Varicella Zoster Injection","volume":"21","author":"R Hornung","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"May","key":"ppat.1009689.ref038","doi-asserted-by":"crossref","first-page":"135287","DOI":"10.1016\/j.neulet.2020.135287","article-title":"Reduced activity of GAD67 expressing cells in the reticular thalamus enhance thalamic excitatory activity and varicella zoster virus associated pain","volume":"736","author":"R Hornung","year":"2020","journal-title":"Neurosci Lett"},{"issue":"9","key":"ppat.1009689.ref039","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.chembiol.2010.07.009","article-title":"A general chemical method to regulate protein stability in the mammalian central nervous system","volume":"17","author":"M Iwamoto","year":"2010","journal-title":"Chem Biol"},{"issue":"8","key":"ppat.1009689.ref040","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1128\/JVI.02137-08","article-title":"The replication cycle of varicella-zoster virus: analysis of the kinetics of viral protein expression, genome synthesis, and virion assembly at the single-cell level","volume":"83","author":"M Reichelt","year":"2009","journal-title":"J Virol"},{"issue":"9","key":"ppat.1009689.ref041","doi-asserted-by":"crossref","first-page":"7073","DOI":"10.1128\/jvi.71.9.7073-7079.1997","article-title":"Varicella-zoster virus open reading frame 4 encodes an immediate-early protein with posttranscriptional regulatory properties","volume":"71","author":"P Defechereux","year":"1997","journal-title":"J Virol"},{"issue":"5","key":"ppat.1009689.ref042","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1128\/jvi.69.5.3240-3245.1995","article-title":"Varicella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency","volume":"69","author":"S Debrus","year":"1995","journal-title":"J Virol"},{"issue":"6","key":"ppat.1009689.ref043","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1128\/jvi.62.6.2076-2082.1988","article-title":"Cell lines containing varicella-zoster virus open reading frame 62 and expressing the \u201cIE\u201d 175 protein complement ICP4 mutants of herpes simplex virus type 1","volume":"62","author":"JM Felser","year":"1988","journal-title":"J Virol"},{"issue":"12","key":"ppat.1009689.ref044","doi-asserted-by":"crossref","first-page":"7303","DOI":"10.1128\/jvi.66.12.7303-7308.1992","article-title":"Varicella-zoster virus open reading frame 61 protein is functionally homologous to herpes simplex virus type 1 ICP0","volume":"66","author":"H Moriuchi","year":"1992","journal-title":"J Virol"},{"issue":"14","key":"ppat.1009689.ref045","doi-asserted-by":"crossref","first-page":"7973","DOI":"10.1128\/JVI.00376-14","article-title":"The varicella-zoster virus portal protein is essential for cleavage and packaging of viral DNA","volume":"88","author":"MA Visalli","year":"2014","journal-title":"J Virol"},{"issue":"1","key":"ppat.1009689.ref046","first-page":"25","article-title":"Development of a live attenuated varicella vaccine","volume":"18","author":"M Takahashi","year":"1975","journal-title":"Biken J"},{"issue":"23","key":"ppat.1009689.ref047","doi-asserted-by":"crossref","first-page":"13200","DOI":"10.1128\/JVI.01148-07","article-title":"A self-excisable infectious bacterial artificial chromosome clone of varicella-zoster virus allows analysis of the essential tegument protein encoded by ORF9","volume":"81","author":"BK Tischer","year":"2007","journal-title":"J Virol"},{"issue":"13","key":"ppat.1009689.ref048","doi-asserted-by":"crossref","first-page":"6220","DOI":"10.1128\/JVI.02396-10","article-title":"Varicella-zoster virus (VZV) infection of neurons derived from human embryonic stem cells: direct demonstration of axonal infection, transport of VZV, and productive neuronal infection","volume":"85","author":"A Markus","year":"2011","journal-title":"J Virol"},{"issue":"2","key":"ppat.1009689.ref049","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2144\/000112096","article-title":"Two-step red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coli","volume":"40","author":"BK Tischer","year":"2006","journal-title":"Biotechniques"},{"issue":"54","key":"ppat.1009689.ref050","first-page":"2","article-title":"Preparation of Viral DNA from Nucleocapsids","author":"ML Szpara","year":"2011","journal-title":"J Vis Exp"},{"issue":"2","key":"ppat.1009689.ref051","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1128\/JVI.72.2.965-974.1998","article-title":"Attenuation of the vaccine Oka strain of varicella-zoster virus and role of glycoprotein C in alphaherpesvirus virulence demonstrated in the SCID-hu mouse","volume":"72","author":"JF Moffat","year":"1998","journal-title":"J Virol"},{"issue":"3","key":"ppat.1009689.ref052","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.vascn.2011.01.003","article-title":"Quantitative immunofluorescent blotting of the Multidrug Resistance-associated Protein 2 (MRP2)","volume":"63","author":"PM Gerk","year":"2011","journal-title":"J Pharmacol Toxicol Methods"},{"issue":"4","key":"ppat.1009689.ref053","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1128\/JVI.80.4.1710-1723.2006","article-title":"Phosphorylation of the varicella-zoster virus (VZV) major transcriptional regulatory protein IE62 by the VZV open reading frame 66 protein kinase","volume":"80","author":"AJ Eisfeld","year":"2006","journal-title":"J Virol"},{"issue":"3","key":"ppat.1009689.ref054","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1128\/jvi.62.3.802-809.1988","article-title":"Identification and characterization of a varicella-zoster virus DNA-binding protein by using antisera directed against a predicted synthetic oligopeptide","volume":"62","author":"PR Kinchington","year":"1988","journal-title":"J Virol"},{"issue":"7","key":"ppat.1009689.ref055","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1128\/jvi.69.7.4274-4282.1995","article-title":"The transcriptional regulatory proteins encoded by varicella-zoster virus open reading frames (ORFs) 4 and 63, but not ORF 61, are associated with purified virus particles","volume":"69","author":"PR Kinchington","year":"1995","journal-title":"J Virol"},{"issue":"1","key":"ppat.1009689.ref056","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/s41467-018-03569-2","article-title":"A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61","volume":"9","author":"DP Depledge","year":"2018","journal-title":"Nat Commun"},{"issue":"62","key":"ppat.1009689.ref057","first-page":"e3247","article-title":"Acute and chronic tactile sensory testing after spinal cord injury in rats","author":"MR Detloff","year":"2012","journal-title":"J Vis Exp"},{"issue":"1","key":"ppat.1009689.ref058","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","article-title":"Quantitative assessment of tactile allodynia in the rat paw","volume":"53","author":"SR Chaplan","year":"1994","journal-title":"J Neurosci Methods"},{"issue":"1","key":"ppat.1009689.ref059","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0304-3959(88)90026-7","article-title":"A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia","volume":"32","author":"K Hargreaves","year":"1988","journal-title":"Pain"},{"issue":"1","key":"ppat.1009689.ref060","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1142\/S0219635212500045","article-title":"The place escape\/avoidance paradigm: a novel method to assess nociceptive processing","volume":"11","author":"PN Fuchs","year":"2012","journal-title":"J Integr Neurosci"},{"issue":"22","key":"ppat.1009689.ref061","doi-asserted-by":"crossref","first-page":"12369","DOI":"10.1128\/JVI.77.22.12369-12372.2003","article-title":"Requirement of varicella-zoster virus immediate-early 4 protein for viral replication","volume":"77","author":"B Sato","year":"2003","journal-title":"J Virol"},{"issue":"21","key":"ppat.1009689.ref062","doi-asserted-by":"crossref","first-page":"11833","DOI":"10.1128\/JVI.78.21.11833-11840.2004","article-title":"The varicella-zoster virus open reading frame 63 latency-associated protein is critical for establishment of latency","volume":"78","author":"JI Cohen","year":"2004","journal-title":"J Virol"},{"issue":"11","key":"ppat.1009689.ref063","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1128\/JVI.79.11.6969-6975.2005","article-title":"Varicella-zoster virus ORF4 latency-associated protein is important for establishment of latency","volume":"79","author":"JI Cohen","year":"2005","journal-title":"J Virol"},{"issue":"5","key":"ppat.1009689.ref064","doi-asserted-by":"crossref","first-page":"e1004901","DOI":"10.1371\/journal.ppat.1004901","article-title":"Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms","volume":"11","author":"MC Verweij","year":"2015","journal-title":"PLoS Pathog"},{"issue":"Pt 3","key":"ppat.1009689.ref065","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1099\/vir.0.027029-0","article-title":"Characterization of the nuclear import and export signals, and subcellular transport mechanism of varicella-zoster virus ORF9","volume":"92","author":"M Cai","year":"2011","journal-title":"J Gen Virol"},{"issue":"1","key":"ppat.1009689.ref066","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1477-5956-8-8","article-title":"Improving the yeast two-hybrid system with permutated fusions proteins: the Varicella Zoster Virus interactome","volume":"8","author":"T Stellberger","year":"2010","journal-title":"Proteome Sci"},{"issue":"5","key":"ppat.1009689.ref067","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1128\/JVI.02757-12","article-title":"ORF9p phosphorylation by ORF47p is crucial for the formation and egress of varicella-zoster virus viral particles","volume":"87","author":"L Riva","year":"2013","journal-title":"J Virol"},{"issue":"7","key":"ppat.1009689.ref068","doi-asserted-by":"crossref","first-page":"4379","DOI":"10.1128\/jvi.67.7.4379-4385.1993","article-title":"Characterization of the regulatory functions of varicella-zoster virus open reading frame 4 gene product","volume":"67","author":"P Defechereux","year":"1993","journal-title":"J Virol"},{"issue":"11","key":"ppat.1009689.ref069","doi-asserted-by":"crossref","first-page":"e7882","DOI":"10.1371\/journal.pone.0007882","article-title":"Varicella-zoster virus IE4 protein interacts with SR proteins and exports mRNAs through the TAP\/NXF1 pathway","volume":"4","author":"I Ote","year":"2009","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1009689.ref070","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s11262-013-1006-z","article-title":"Nuclear localization signals of varicella zoster virus ORF4","volume":"48","author":"Y Huang","year":"2014","journal-title":"Virus Genes"},{"issue":"23","key":"ppat.1009689.ref071","doi-asserted-by":"crossref","first-page":"21050","DOI":"10.1074\/jbc.M111872200","article-title":"Phosphorylation of varicella-zoster virus IE63 protein by casein kinases influences its cellular localization and gene regulation activity","volume":"277","author":"S Bontems","year":"2002","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1009689.ref072","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1128\/jvi.70.1.658-662.1996","article-title":"Phosphorylation and nuclear localization of the varicella-zoster virus gene 63 protein","volume":"70","author":"D Stevenson","year":"1996","journal-title":"J Virol"},{"issue":"1","key":"ppat.1009689.ref073","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.virol.2004.02.020","article-title":"Varicella-Zoster virus proteins encoded by open reading frames 14 and 67 are both dispensable for the establishment of latency in a rat model","volume":"323","author":"E Grinfeld","year":"2004","journal-title":"Virology"},{"issue":"12","key":"ppat.1009689.ref074","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.jfma.2013.05.013","article-title":"Attenuation of neuropathic pain by sodium butyrate in an experimental model of chronic constriction injury in rats","volume":"113","author":"A Kukkar","year":"2014","journal-title":"J Formos Med Assoc"},{"key":"ppat.1009689.ref075","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.phrs.2015.11.026","article-title":"Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice","volume":"103","author":"R Russo","year":"2016","journal-title":"Pharmacol Res"},{"key":"ppat.1009689.ref076","article-title":"Comparison of Different Histone Deacetylase Inhibitors in Attenuating Inflammatory Pain in Rats","volume":"2019","author":"Y Mao","year":"2019","journal-title":"Pain Res Manag"},{"issue":"15","key":"ppat.1009689.ref077","doi-asserted-by":"crossref","first-page":"7844","DOI":"10.1128\/JVI.00325-07","article-title":"Varicella-Zoster virus IE63, a major viral latency protein, is required to inhibit the alpha interferon-induced antiviral response","volume":"81","author":"APN Ambagala","year":"2007","journal-title":"J Virol"},{"issue":"17","key":"ppat.1009689.ref078","doi-asserted-by":"crossref","first-page":"8224","DOI":"10.1128\/JVI.75.17.8224-8239.2001","article-title":"Mutational analysis of the repeated open reading frames, ORFs 63 and 70 and ORFs 64 and 69, of varicella-zoster virus","volume":"75","author":"MH Sommer","year":"2001","journal-title":"J Virol"},{"issue":"7","key":"ppat.1009689.ref079","doi-asserted-by":"crossref","first-page":"e1000971","DOI":"10.1371\/journal.ppat.1000971","article-title":"Genome-Wide Mutagenesis Reveals That ORF7 Is a Novel VZV Skin-Tropic Factor","volume":"6","author":"Z Zhang","year":"2010","journal-title":"PLoS Pathog"},{"issue":"2","key":"ppat.1009689.ref080","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1080\/13550280390194000","article-title":"Herpes simplex virus-1 and varicella-zoster virus latency in ganglia","volume":"9","author":"BM Mitchell","year":"2003","journal-title":"J Neurovirol"},{"issue":"4","key":"ppat.1009689.ref081","first-page":"277","article-title":"Rodent models of varicella-zoster virus neurotropism","volume":"342","author":"JI Cohen","year":"2010","journal-title":"Curr Top Microbiol Immunol"},{"issue":"10","key":"ppat.1009689.ref082","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/j.1532-2149.2012.00140.x","article-title":"The correlation between pain-related behaviour and spinal microgliosis in four distinct models of peripheral neuropathy","volume":"16","author":"J Blackbeard","year":"2012","journal-title":"Eur J Pain"},{"issue":"1","key":"ppat.1009689.ref083","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.pain.2007.11.006","article-title":"Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain","volume":"138","author":"SJ Medhurst","year":"2008","journal-title":"Pain"},{"issue":"1","key":"ppat.1009689.ref084","doi-asserted-by":"crossref","first-page":"11234","DOI":"10.1038\/srep11234","article-title":"The structure of the folded domain from the signature multifunctional protein ICP27 from herpes simplex virus-1 reveals an intertwined dimer","volume":"5","author":"RB Tunnicliffe","year":"2015","journal-title":"Sci Rep"},{"issue":"8","key":"ppat.1009689.ref085","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1128\/JVI.02592-07","article-title":"Mechanisms of varicella-zoster virus neuropathogenesis in human dorsal root ganglia","volume":"82","author":"M Reichelt","year":"2008","journal-title":"J Virol"},{"issue":"35","key":"ppat.1009689.ref086","doi-asserted-by":"crossref","first-page":"14086","DOI":"10.1073\/pnas.0706023104","article-title":"Aberrant infection and persistence of varicella-zoster virus in human dorsal root ganglia in vivo in the absence of glycoprotein I","volume":"104","author":"L Zerboni","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5899","key":"ppat.1009689.ref087","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1126\/science.1164164","article-title":"Noncytotoxic Lytic Granule-Mediated CD8+ T Cell Inhibition of HSV-1 Reactivation from Neuronal Latency","volume":"322","author":"JE Knickelbein","year":"2008","journal-title":"Science (80-)"},{"issue":"2","key":"ppat.1009689.ref088","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1128\/JVI.74.2.1029-1032.2000","article-title":"Granzyme A, a noncytolytic component of CD8(+) cell granules, restricts the spread of herpes simplex virus in the peripheral nervous systems of experimentally infected mice","volume":"74","author":"RA Pereira","year":"2000","journal-title":"J Virol"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009689","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T17:26:38Z","timestamp":1625592398000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009689"}},"subtitle":[],"editor":[{"given":"Ann","family":"Arvin","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":88,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009689","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,6]]}}}