{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:32:16Z","timestamp":1791844336768,"version":"4.3.4"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"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":["RTG1949"],"award-info":[{"award-number":["RTG1949"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Type I interferons (IFNs) present the first line of defense against viral infections, providing antiviral, immunomodulatory and antiproliferative effects. The type I IFN family contains 12 IFN\u03b1 subtypes and IFN\u03b2, and although they share the same receptor, they are classified as non-redundant, capable to induce a variety of different IFN-stimulated genes. However, the biological impact of individual subtypes remains controversial. Recent data propose a subtype-specificity of type I IFNs revealing unique effector functions for different viruses and thus expanding the implications for IFN\u03b1-based antiviral immunotherapies. Despite extensive research, drug-resistant infections with herpes simplex virus type 1 (HSV-1), which is the common agent of recurrent orogenital lesions, are still lacking a protective or curing therapeutic. However, due to the risk of generalized infections in immunocompromised hosts as well as the increasing incidence of resistance to conventional antiherpetic agents, HSV infections raise major health concerns. Based on their pleiotropic effector functions, the application of type I IFNs represents a promising approach to inhibit HSV-1 replication, to improve host immunity and to further elucidate their qualitative differences. Here, selective IFN\u03b1 subtypes and IFN\u03b2 were evaluated for their therapeutic potential in genital HSV-1 infections. Respective<jats:italic>in vivo<\/jats:italic>studies in mice revealed subtype-specific differences in the reduction of local viral loads. IFN\u03b2 had the strongest antiviral efficacy against genital HSV-1 infection in mice, whereas IFN\u03b11, IFN\u03b14, and IFN\u03b111 had no impact on viral loads. Based on flow cytometric analyses of underlying immune responses at local and peripheral sites, these differences could be further assigned to specific modulations of the antiviral immunity early during HSV-1 infection. IFN\u03b2 led to enhanced systemic cytokine secretion and elevated cytotoxic responses, which negatively correlated with viral loads in the vaginal tract. These data provide further insights into the diversity of type I IFN effector functions and their impact on the immunological control of HSV-1 infections.<\/jats:p>","DOI":"10.3389\/fcimb.2022.949036","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T05:51:42Z","timestamp":1665985902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Superior antiviral activity of IFN\u03b2 in genital HSV-1 infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Yasmin","family":"Schmitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Schwerdtfeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaana","family":"Westmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Littwitz-Salomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Alt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Brochhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalbert","family":"Krawczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Sutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00139","article-title":"Current antivirals and novel botanical molecules interfering with herpes simplex virus infection","volume":"11","author":"\u00c1lvarez","year":"2020","journal-title":"Front. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1251\/bpo118","article-title":"Direct application of plasmid DNA containing type I interferon transgenes to vaginal mucosa inhibits HSV-2 mediated mortality","volume":"8","author":"Austin","year":"2006","journal-title":"Biol. Proced Online"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.4049\/jimmunol.175.2.1100","article-title":"Critical role for the oligoadenylate synthetase\/RNase l pathway in response to IFN-beta during acute ocular herpes simplex virus type 1 infection","volume":"175","author":"Austin","year":"2005","journal-title":"J. Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"8146","DOI":"10.1073\/pnas.97.14.8146","article-title":"Retrograde axonal transport of herpes simplex virus: evidence for a single mechanism and a role for tegument","volume":"97","author":"Bearer","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B5","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1056\/NEJMoa1103151","article-title":"Efficacy results of a trial of a herpes simplex vaccine","volume":"366","author":"Belshe","year":"2012","journal-title":"N Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.jim.2005.08.005","article-title":"Virus free, cell-based assay for the quantification of murine type I interferons","volume":"306","author":"Bollati-Fogolin","year":"2005","journal-title":"J. Immunol. Methods"},{"key":"B7","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1182\/blood-2007-09-077438","article-title":"Human natural killer cells","volume":"112","author":"Caligiuri","year":"2008","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1159\/000009998","article-title":"Treatment of recurrent genital herpes with interferon alpha-2alpha","volume":"46","author":"Cardamakis","year":"1998","journal-title":"Gynecol. Obstet. Invest."},{"key":"B9","doi-asserted-by":"publisher","first-page":"9398","DOI":"10.1128\/JVI.76.18.9398-9406.2002","article-title":"The antiviral efficacy of the murine alpha-1 interferon transgene against ocular herpes simplex virus type 1 requires the presence of CD4(+), alpha\/beta T-cell receptor-positive T lymphocytes with the capacity to produce gamma interferon","volume":"76","author":"Carr","year":"2002","journal-title":"J. Virol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"9341","DOI":"10.1128\/JVI.79.14.9341-9345.2005","article-title":"RNA-Dependent protein kinase is required for alpha-1 interferon transgene-induced resistance to genital herpes simplex virus type 2","volume":"79","author":"Carr","year":"2005","journal-title":"J. Virol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1089\/jir.2004.24.687","article-title":"Diversity and relatedness among the type I interferons","volume":"24","author":"Chen","year":"2004","journal-title":"J. Interferon Cytokine Res."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94366","article-title":"Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection","volume":"2","author":"Cheng","year":"2017","journal-title":"JCI Insight"},{"key":"B13","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/hep.31282","article-title":"Functional comparison of interferon-\u03b1 subtypes reveals potent hepatitis b virus suppression by a concerted action of interferon-\u03b1 and interferon-\u03b3 signaling","volume":"73","author":"Chen","year":"2021","journal-title":"Hepatology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"979","DOI":"10.3390\/v1030979","article-title":"Innate and adaptive immune responses to herpes simplex virus","volume":"1","author":"Chew","year":"2009","journal-title":"Viruses"},{"key":"B15","doi-asserted-by":"publisher","first-page":"958","DOI":"10.7326\/0003-4819-98-6-958","article-title":"Genital herpes simplex virus infections: clinical manifestations, course, and complications","volume":"98","author":"Corey","year":"1983","journal-title":"Ann. Intern. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1006\/viro.1999.9613","article-title":"Resistance to herpetic stromal keratitis in immunized b-cell-deficient mice","volume":"257","author":"Daheshia","year":"1999","journal-title":"Virology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"5150","DOI":"10.3390\/ijms21145150","article-title":"Herpes simplex virus type 1 interactions with the interferon system","volume":"21","author":"Danastas","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1128\/JCM.42.1.242-249.2004","article-title":"Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up","volume":"42","author":"Danve-Szatanek","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3864","DOI":"10.1038\/ncomms4864","article-title":"Pathogenic potential of interferon \u03b1\u03b2 in acute influenza infection","volume":"5","author":"Davidson","year":"2014","journal-title":"Nat. Commun."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02255","article-title":"Diverse immunomodulatory effects of individual IFN\u03b1 subtypes on virus-specific CD8(+) T cell responses","volume":"10","author":"Dickow","year":"2019","journal-title":"Front. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.jaad.2007.06.027","article-title":"Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management","volume":"57","author":"Fatahzadeh","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.724618","article-title":"Immunoregulatory functions of interferons during genital HSV-2 infection","volume":"12","author":"Feng","year":"2021","journal-title":"Front. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1089\/jir.2013.0118","article-title":"High-density nucleosome occupancy map of human chromosome 9p21-22 reveals chromatin organization of the type I interferon gene cluster","volume":"34","author":"Freaney","year":"2014","journal-title":"J. Interferon Cytokine Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1126\/science.1233321","article-title":"Interferon-epsilon protects the female reproductive tract from viral and bacterial infection","volume":"339","author":"Fung","year":"2013","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/eji.200838311","article-title":"Anti-retroviral effects of type I IFN subtypes in vivo","volume":"39","author":"Gerlach","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002868","article-title":"Interferon-alpha subtype 11 activates NK cells and enables control of retroviral infection","volume":"8","author":"Gibbert","year":"2012","journal-title":"PloS Pathog."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1111\/bph.12010","article-title":"IFN-alpha subtypes: distinct biological activities in anti-viral therapy","volume":"168","author":"Gibbert","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.cellimm.2011.03.007","article-title":"NK cells require type I IFN receptor for antiviral responses during genital HSV-2 infection","volume":"269","author":"Gill","year":"2011","journal-title":"Cell Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.1128\/JVI.79.5.3107-3116.2005","article-title":"Estradiol regulates susceptibility following primary exposure to genital herpes simplex virus type 2, while progesterone induces inflammation","volume":"79","author":"Gillgrass","year":"2005","journal-title":"J. Virol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00921-20","article-title":"The innate immune response to herpes simplex virus 1 infection is dampened in the newborn brain and can be modulated by exogenous interferon beta to improve survival","volume":"11","author":"Giraldo","year":"2020","journal-title":"mBio"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008986","article-title":"Qualitative differences between the IFN\u03b1 subtypes and IFN\u03b2 influence chronic mucosal HIV-1 pathogenesis","volume":"16","author":"Guo","year":"2020","journal-title":"PloS Pathog."},{"key":"B32","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1128\/JVI.02137-15","article-title":"Interferon kappa inhibits human papillomavirus 31 transcription by inducing Sp100 proteins","volume":"90","author":"Habiger","year":"2016","journal-title":"J. Virol."},{"key":"B33","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.4049\/jimmunol.133.5.2743","article-title":"In vivo significance of NK cell on resistance against virus (HSV-1) infections in mice","volume":"133","author":"Habu","year":"1984","journal-title":"J. Immunol."},{"key":"B34","doi-asserted-by":"crossref","first-page":"118","DOI":"10.33590\/emjdermatol\/10311121","article-title":"A systematic review on the efficacy of topical acyclovir, penciclovir, and docosanol for the treatment of herpes simplex labialis","volume":"6","author":"Hammer","year":"2018","journal-title":"EMJ Dermatol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"6558","DOI":"10.1128\/JVI.76.13.6558-6567.2002","article-title":"Differential effect of murine alpha\/beta interferon transgenes on antagonization of herpes simplex virus type 1 replication","volume":"76","author":"H\u00e4rle","year":"2002","journal-title":"J. Virol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0166-3542(02)00093-1","article-title":"Transient transfection of mouse fibroblasts with type I interferon transgenes provides various degrees of protection against herpes simplex virus infection","volume":"56","author":"H\u00e4rle","year":"2002","journal-title":"Antiviral Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.4049\/jimmunol.166.3.1803","article-title":"The application of a plasmid DNA encoding IFN-alpha 1 postinfection enhances cumulative survival of herpes simplex virus type 2 vaginally infected mice","volume":"166","author":"H\u00e4rle","year":"2001","journal-title":"J. Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1006\/viro.2001.1280","article-title":"The immediate-early protein, ICP0, is essential for the resistance of herpes simplex virus to interferon-alpha\/beta","volume":"293","author":"Harle","year":"2002","journal-title":"Virology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.prp.2004.12.003","article-title":"Generalized herpes simplex virus infection in an immunocompromised patient\u2013report of a case and review of the literature","volume":"201","author":"Herget","year":"2005","journal-title":"Pathol. Res. Pract."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1158\/1078-0432.CCR-10-1114","article-title":"Direct effects of type I interferons on cells of the immune system","volume":"17","author":"Hervas-Stubbs","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/B978-012465330-6\/50003-8","article-title":"Virus isolation and quantitation","author":"Hierholzer","year":"1996","journal-title":"Virol. Methods Man"},{"key":"B42","doi-asserted-by":"publisher","first-page":"158s","DOI":"10.1111\/1523-1747.ep12875164","article-title":"Interferon as an agent against herpes simplex virus","volume":"95","author":"Ho","year":"1990","journal-title":"J. Invest. Dermatol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2471\/BLT.19.237149","article-title":"Herpes simplex virus: global infection prevalence and incidence estimates, 2016","volume":"98","author":"James","year":"2020","journal-title":"Bull. World Health Organ"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3791\/4391","article-title":"Isolation of lymphocytes from mouse genital tract mucosa","volume":"67","author":"Jiang","year":"2012","journal-title":"J. Vis. Exp."},{"key":"B45","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/S0140-6736(76)92850-6","article-title":"Topical therapy of ulcerative herpetic keratitis with human interferon","volume":"2","author":"Jones","year":"1976","journal-title":"Lancet"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010688","article-title":"Swarms of chemically modified antiviral siRNA targeting herpes simplex virus infection in human corneal epithelial cells","volume":"18","author":"Kalke","year":"2022","journal-title":"PloS Pathog."},{"key":"B47","doi-asserted-by":"publisher","first-page":"4558","DOI":"10.1128\/JVI.77.8.4558-4565.2003","article-title":"Progesterone increases susceptibility and decreases immune responses to genital herpes infection","volume":"77","author":"Kaushic","year":"2003","journal-title":"J. Virol."},{"key":"B48","doi-asserted-by":"publisher","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":"B49","doi-asserted-by":"publisher","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":"Knickelbein","year":"2008","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1146\/annurev.med.59.061606.095540","article-title":"Herpes simplex: insights on pathogenesis and possible vaccines","volume":"59","author":"Koelle","year":"2008","journal-title":"Annu. Rev. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1093\/infdis\/154.3.437","article-title":"Suppression of recurrent genital herpes simplex virus infection with recombinant alpha 2 interferon","volume":"154","author":"Kuhls","year":"1986","journal-title":"J. Infect. Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/978-3-319-53168-7_3","article-title":"Innate immune mechanisms and herpes simplex virus infection and disease","volume":"223","author":"Kurt-Jones","year":"2017","journal-title":"Adv. Anat Embryol Cell Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"6001","DOI":"10.1128\/JVI.00451-16","article-title":"Interferon alpha subtype-specific suppression of HIV-1 infection in vivo","volume":"90","author":"Lavender","year":"2016","journal-title":"J. Virol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.jaad.2007.02.008","article-title":"A meta-analysis to assess the efficacy of oral antiviral treatment to prevent genital herpes outbreaks","volume":"57","author":"Lebrun-Vignes","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"5084682","DOI":"10.1155\/2020\/5084682","article-title":"Interferon kappa is important for keratinocyte host defense against herpes simplex virus-1","volume":"2020","author":"Li","year":"2020","journal-title":"J. Immunol. Res."},{"key":"B56","doi-asserted-by":"publisher","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":"B57","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1136\/sti.2004.012039","article-title":"A systematic review of the epidemiology and interaction of herpes simplex virus types 1 and 2","volume":"81","author":"Looker","year":"2005","journal-title":"Sex Transm Infect."},{"key":"B58","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/s41564-019-0421-x","article-title":"And III interferon signalling during viral infection","volume":"4","author":"Mesev","year":"2019","journal-title":"Nat. Microbiol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3390\/pathogens11080853","article-title":"Interferon epsilon signaling confers attenuated zika replication in human vaginal epithelial cells","volume":"11","author":"Mungin","year":"2022","journal-title":"Pathogens"},{"key":"B60","doi-asserted-by":"publisher","first-page":"10820","DOI":"10.1128\/JVI.00365-08","article-title":"Natural killer cells as novel helpers in anti-herpes simplex virus immune response","volume":"82","author":"Nandakumar","year":"2008","journal-title":"J. Virol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"6435","DOI":"10.4049\/jimmunol.164.12.6435","article-title":"Plasmid DNA encoding IFN-alpha 1 antagonizes herpes simplex virus type 1 ocular infection through CD4+ and CD8+ T lymphocytes","volume":"164","author":"Noisakran","year":"2000","journal-title":"J. Immunol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"754","DOI":"10.2165\/00003495-199652050-00009","article-title":"Valaciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections","volume":"52","author":"Perry","year":"1996","journal-title":"Drugs"},{"key":"B63","doi-asserted-by":"publisher","first-page":"11372","DOI":"10.1128\/JVI.05279-11","article-title":"High-risk human papillomaviruses repress constitutive kappa interferon transcription via E6 to prevent pathogen recognition receptor and antiviral-gene expression","volume":"85","author":"Reiser","year":"2011","journal-title":"J. Virol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1615\/CritRevImmunol.v30.i2.30","article-title":"Treatment of hepatitis c virus infection with interferon and small molecule direct antivirals: viral kinetics and modeling","volume":"30","author":"Rong","year":"2010","journal-title":"Crit. Rev. Immunol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"11541","DOI":"10.1128\/JVI.76.22.11541-11550.2002","article-title":"Alpha\/Beta interferon and gamma interferon synergize to inhibit the replication of herpes simplex virus type 1","volume":"76","author":"Sainz","year":"2002","journal-title":"J. Virol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.3851\/IMP1870","article-title":"Novel resistance-associated mutations of thymidine kinase and DNA polymerase genes of herpes simplex virus type 1 and type 2","volume":"16","author":"Sauerbrei","year":"2011","journal-title":"Antivir Ther."},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2111600119","article-title":"Differential interferon-alpha subtype induced immune signatures are associated with suppression of SARS-CoV-2 infection","volume":"119","author":"Schuhenn","year":"2022","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B68","doi-asserted-by":"publisher","first-page":"507","DOI":"10.2165\/00003495-200262030-00009","article-title":"Interferon-alpha-2b plus ribavirin: a review of its use in the management of chronic hepatitis c","volume":"62","author":"Scott","year":"2002","journal-title":"Drugs"},{"key":"B69","doi-asserted-by":"publisher","first-page":"13346","DOI":"10.1038\/ncomms13346","article-title":"CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2","volume":"7","author":"Shin","year":"2016","journal-title":"Nat. Commun."},{"key":"B70","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1056\/NEJM197707142970201","article-title":"The natural history of recurrent herpes simplex labialis: implications for antiviral therapy","volume":"297","author":"Spruance","year":"1977","journal-title":"N Engl. J. Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jcv.2004.04.002","article-title":"Survey of acyclovir-resistant herpes simplex virus in the Netherlands: prevalence and characterization","volume":"32","author":"Str\u00e1nsk\u00e1","year":"2005","journal-title":"J. Clin. Virol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.coviro.2016.01.001","article-title":"Type I interferons in viral control and immune regulation","volume":"16","author":"Teijaro","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1016\/S0002-9440(10)63575-4","article-title":"Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response","volume":"163","author":"Theil","year":"2003","journal-title":"Am. J. Pathol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.cell.2011.06.048","article-title":"Structural linkage between ligand discrimination and receptor activation by type I interferons","volume":"146","author":"Thomas","year":"2011","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00373","article-title":"Mechanisms of immune control of mucosal HSV infection: A guide to rational vaccine design","volume":"10","author":"Truong","year":"2019","journal-title":"Front. Immunol."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01882-18","article-title":"Expansion\/Survival cytokines, and JAK\/STAT gene signatures of multifunctional herpes simplex virus-specific effector memory CD8(+) T(EM) cells are associated with asymptomatic herpes in humans","volume":"93","author":"Vahed","year":"2019","journal-title":"J. Virol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/S0140-6736(00)04638-9","article-title":"Herpes simplex virus infections","volume":"357","author":"Whitley","year":"2001","journal-title":"Lancet"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.605673","article-title":"Shared and unique features of human interferon-beta and interferon-alpha subtypes","volume":"11","author":"Wittling","year":"2020","journal-title":"Front. Immunol."},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01714-17","article-title":"Induction of interferon kappa in human papillomavirus 16 infection by transforming growth factor beta-induced promoter demethylation","volume":"92","author":"Woodby","year":"2018","journal-title":"J. Virol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"159","DOI":"10.21037\/atm.2017.03.69","article-title":"Alpha-interferon treatment in hepatitis b","volume":"5","author":"Woo","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2054","article-title":"Characteristics of herpes simplex virus infection and pathogenesis suggest a strategy for vaccine development","volume":"29","author":"Xu","year":"2019","journal-title":"Rev. Med. Virol."},{"key":"B82","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.4049\/jimmunol.146.4.1341","article-title":"Functional heterogeneity among herpes simplex virus-specific human CD4+ T cells","volume":"146","author":"Yasukawa","year":"1991","journal-title":"J. Immunol."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.733364","article-title":"Current and future perspectives","volume":"12","author":"Ye","year":"2021","journal-title":"Front. Immunol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.1182\/blood-2009-03-208736","article-title":"The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response","volume":"114","author":"Zelinskyy","year":"2009","journal-title":"Blood"},{"key":"B85","doi-asserted-by":"publisher","first-page":"2658","DOI":"10.1002\/eji.200636059","article-title":"Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during friend retrovirus infection","volume":"36","author":"Zelinskyy","year":"2006","journal-title":"Eur. J. Immunol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.949036\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T15:07:58Z","timestamp":1678288078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.949036\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":85,"alternative-id":["10.3389\/fcimb.2022.949036"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.949036","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]},"article-number":"949036"}}