{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:18:55Z","timestamp":1790263135695,"version":"4.1.0"},"reference-count":124,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T00:00:00Z","timestamp":1550620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Over the past decades, infection of mice with lymphocytic choriomeningitis virus (LCMV) has provided an invaluable insight into our understanding of immune responses to viruses. In particular, this model has clarified the central roles that type I interferons play in initiating and regulating host responses. The use of different strains of LCMV and routes of infection has allowed us to understand how type I interferons are critical in controlling virus replication and fostering effective antiviral immunity, but also how they promote virus persistence and functional exhaustion of the immune response. Accordingly, these discoveries have formed the foundation for the development of novel treatments for acute and chronic viral infections and even extend into the management of malignant tumors. Here we review the fundamental insights into type I interferon biology gained using LCMV as a model and how the diversity of LCMV strains, dose, and route of administration have been used to dissect the molecular mechanisms underpinning acute versus persistent infection. We also identify gaps in the knowledge regarding LCMV regulation of antiviral immunity. Due to its unique properties, LCMV will continue to remain a vital part of the immunologists\u2019 toolbox.<\/jats:p>","DOI":"10.3390\/v11020172","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T11:45:39Z","timestamp":1550663139000},"page":"172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Complexities of Type I Interferon Biology: Lessons from LCMV"],"prefix":"10.3390","volume":"11","author":[{"given":"Tamara","family":"Suprunenko","sequence":"first","affiliation":[{"name":"School of Life and Environmental Sciences, the Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, and the Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5111-3978","authenticated-orcid":false,"given":"Markus J.","family":"Hofer","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, the Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, and the Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.2741\/3021","article-title":"Lymphocytic choriomeningitis infection of the central nervous system","volume":"13","author":"Kang","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1538\/expanim.16-0097","article-title":"Difference of two new LCMV strains in lethality and viral genome load in tissues","volume":"66","author":"Takagi","year":"2017","journal-title":"Exp. Anim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1084\/jem.160.2.521","article-title":"Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence","volume":"160","author":"Ahmed","year":"1984","journal-title":"J. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1126\/science.81.2099.298","article-title":"A FILTERABLE VIRUS RECOVERED FROM WHITE MICE","volume":"81","author":"Traub","year":"1935","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1126\/science.81.2105.439.b","article-title":"MENINGITIS IN MAN CAUSED BY A FILTERABLE VIRUS","volume":"81","author":"Rivers","year":"1935","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.3201\/eid1607.091902","article-title":"High diversity and ancient common ancestry of lymphocytic choriomeningitis virus","volume":"16","author":"Albarino","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1084\/jem.156.1.79","article-title":"Lymphocytic choriomeningitis virus killer T cells are lethal only in weakly disseminated murine infections","volume":"156","author":"Pfau","year":"1982","journal-title":"J. Exp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8988","DOI":"10.1128\/jvi.70.12.8438-8443.1996","article-title":"Variants able to cause growth hormone deficiency syndrome are present within the disease-nil WE strain of lymphocytic choriomeningitis virus","volume":"70","author":"Teng","year":"1996","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1126\/science.1235214","article-title":"Persistent LCMV infection is controlled by blockade of type I interferon signaling","volume":"340","author":"Teijaro","year":"2013","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.chom.2012.05.003","article-title":"Timing and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection","volume":"11","author":"Wang","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature10624","article-title":"Natural killer cells act as rheostats modulating antiviral T cells","volume":"481","author":"Waggoner","year":"2011","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E7814","DOI":"10.1073\/pnas.1804674115","article-title":"Lymphocytic choriomeningitis virus Clone 13 infection causes either persistence or acute death dependent on IFN-1, cytotoxic T lymphocytes (CTLs), and host genetics","volume":"115","author":"Oldstone","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.4049\/jimmunol.177.5.3266","article-title":"Type 1 IFN deficiency in the absence of normal splenic architecture during lymphocytic choriomeningitis virus infection","volume":"177","author":"Louten","year":"2006","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.2307\/4581290","article-title":"Experimental Lymphocytic Choriomeningitis of Monkeys and Mice Produced by a Virus Encountered in Studies of the 1933 St. Louis Encephalitis Epidemic","volume":"49","author":"Armstrong","year":"1934","journal-title":"Public Health Reports (1896\u20131970)"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1099\/0022-1317-64-8-1689","article-title":"Genomic and biological variation among commonly used lymphocytic choriomeningitis virus strains","volume":"64","author":"Dutko","year":"1983","journal-title":"J. Gen. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1128\/jvi.68.3.1951-1955.1994","article-title":"Resistance of lymphocytic choriomeningitis virus to alpha\/beta interferon and to gamma interferon","volume":"68","author":"Moskophidis","year":"1994","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1084\/jem.138.5.1266","article-title":"Cytotoxic thymus-derived lymphocytes in cerebrospinal fluid of mice with lymphocytic choriomeningitis","volume":"138","author":"Zinkernagel","year":"1973","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/eji.1830160413","article-title":"Induction or prevention of immunopathological disease by cloned cytotoxic T cell lines specific for lymphocytic choriomeningitis virus","volume":"16","author":"Baenziger","year":"1986","journal-title":"Eur. J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8407","DOI":"10.1128\/JVI.75.18.8407-8423.2001","article-title":"Critical role for alpha\/beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic T cells","volume":"75","author":"Ou","year":"2001","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0165-5728(98)00055-1","article-title":"Role of interferon-gamma in the pathogenesis of LCMV-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-gamma knock-out mice","volume":"86","author":"Nansen","year":"1998","journal-title":"J. Neuroimmunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"608","DOI":"10.4049\/jimmunol.134.1.608","article-title":"Mechanism of recovery from acute virus infection. I. Role of T lymphocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice","volume":"134","author":"Assmann","year":"1985","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1600-065X.1993.tb01517.x","article-title":"Effector T-cell induction and T-cell memory versus peripheral deletion of T cells","volume":"133","author":"Zinkernagel","year":"1993","journal-title":"Immunol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/2221045a0","article-title":"Antibody formation in persistent tolerant infection with lymphocytic choriomeningitis virus","volume":"222","author":"Benson","year":"1969","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"392","DOI":"10.4049\/jimmunol.86.4.392","article-title":"Studies of Lymphocytic Choriomeningitis in Mice I. The Relationship Between Age at Inoculation and Outcome of Infection","volume":"86","author":"Hotchin","year":"1961","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1099\/0022-1317-64-8-1827","article-title":"Lethal role of interferon in lymphocytic choriomeningitis virus-induced encephalitis","volume":"64","author":"Pfau","year":"1983","journal-title":"J. Gen. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1099\/0022-1317-37-1-85","article-title":"A new method to detect lymphocytic choriomeningitis virus-specific antibody in human sera","volume":"37","author":"Ambrassat","year":"1977","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1128\/jvi.67.1.332-339.1993","article-title":"Antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking CD8+ T lymphocytes because of disruption of the beta 2-microglobulin gene","volume":"67","author":"Lohler","year":"1993","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1128\/jvi.51.3.682-686.1984","article-title":"Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo","volume":"51","author":"Byrne","year":"1984","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1126\/science.8009221","article-title":"Functional role of type I and type II interferons in antiviral defense","volume":"264","author":"Steinhoff","year":"1994","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1365-3083.1994.tb03477.x","article-title":"The role of CD4+ T cells in cell-mediated immunity to LCMV: Studies in MHC class I and class II deficient mice","volume":"40","author":"Christensen","year":"1994","journal-title":"Scand. J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.4049\/jimmunol.138.7.2278","article-title":"Functional analysis of T lymphocyte subsets in antiviral host defense","volume":"138","author":"Leist","year":"1987","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1084\/jem.188.12.2205","article-title":"Viral immune evasion due to persistence of activated T cells without effector function","volume":"188","author":"Zajac","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.it.2015.02.008","article-title":"Overcoming T cell exhaustion in infection and cancer","volume":"36","author":"Pauken","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12964-016-0160-z","article-title":"T cell exhaustion: from pathophysiological basics to tumor immunotherapy","volume":"15","author":"Catakovic","year":"2017","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21641","DOI":"10.1073\/pnas.1011998107","article-title":"Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression","volume":"107","author":"Bergthaler","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1126\/science.282.5396.2079","article-title":"Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus","volume":"282","author":"Cao","year":"1998","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1084\/jem.192.9.1249","article-title":"Immunosuppression and resultant viral persistence by specific viral targeting of dendritic cells","volume":"192","author":"Sevilla","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1172\/JCI20243","article-title":"Viral targeting of hematopoietic progenitors and inhibition of DC maturation as a dual strategy for immune subversion","volume":"113","author":"Sevilla","year":"2004","journal-title":"J. Clin. Invest."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.coviro.2011.05.006","article-title":"The role of dendritic cells in viral persistence","volume":"1","author":"Ng","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.virol.2004.05.009","article-title":"Use of alternative receptors different than alpha-dystroglycan by selected isolates of lymphocytic choriomeningitis virus","volume":"325","author":"Kunz","year":"2004","journal-title":"Virology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1128\/JVI.75.1.448-457.2001","article-title":"Differences in affinity of binding of lymphocytic choriomeningitis virus strains to the cellular receptor alpha-dystroglycan correlate with viral tropism and disease kinetics","volume":"75","author":"Smelt","year":"2001","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.4049\/jimmunol.1103656","article-title":"Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection","volume":"188","author":"Clingan","year":"2012","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1128\/JVI.01331-07","article-title":"Cellular entry of lymphocytic choriomeningitis virus","volume":"82","author":"Rojek","year":"2008","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.virol.2004.01.033","article-title":"Does Toll-like receptor 3 play a biological role in virus infections?","volume":"322","author":"Edelmann","year":"2004","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jneuroim.2007.11.018","article-title":"Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88\/Mal-dependent inflammatory responses","volume":"194","author":"Zhou","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/eji.200425730","article-title":"MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection","volume":"35","author":"Zhou","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.immuni.2010.03.012","article-title":"Intracellular toll-like receptors","volume":"32","author":"Blasius","year":"2010","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/ni1118","article-title":"Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6","volume":"5","author":"Kawai","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nri2358","article-title":"Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases","volume":"8","author":"Gilliet","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9452","DOI":"10.1128\/JVI.00155-10","article-title":"Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus","volume":"84","author":"Zhou","year":"2010","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0014-5793(98)00210-5","article-title":"Involvement of the IRF family transcription factor IRF-3 in virus-induced activation of the IFN-beta gene","volume":"425","author":"Sato","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1093\/emboj\/17.22.6660","article-title":"Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7","volume":"17","author":"Marie","year":"1998","journal-title":"EMBO J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.cytogfr.2014.05.004","article-title":"RIG-I-like receptors and negative-strand RNA viruses: RLRly bird catches some worms","volume":"25","author":"Weber","year":"2014","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0014-5793(98)01514-2","article-title":"Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7","volume":"441","author":"Sato","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15495","DOI":"10.1074\/jbc.M212940200","article-title":"Interferon regulatory factor-7 synergizes with other transcription factors through multiple interactions with p300\/CBP coactivators","volume":"278","author":"Yang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9192","DOI":"10.1128\/JVI.00555-06","article-title":"Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus","volume":"80","author":"Zuniga","year":"2006","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8219","DOI":"10.1128\/JVI.78.15.8219-8228.2004","article-title":"Characterization of the murine alpha interferon gene family","volume":"78","author":"Lanaya","year":"2004","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.0105-2896.2004.00204.x","article-title":"Interferons, interferon-like cytokines, and their receptors","volume":"202","author":"Pestka","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/imr.12001","article-title":"Structural and dynamic determinants of type I interferon receptor assembly and their functional interpretation","volume":"250","author":"Piehler","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.chom.2015.04.005","article-title":"Blockade of interferon Beta, but not interferon alpha, signaling controls persistent viral infection","volume":"17","author":"Ng","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8555","DOI":"10.1073\/pnas.87.21.8555","article-title":"ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains","volume":"87","author":"Fu","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1101\/gad.3.9.1362","article-title":"Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro","volume":"3","author":"Levy","year":"1989","journal-title":"Genes Dev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3389\/fimmu.2017.00029","article-title":"Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses","volume":"8","author":"Majoros","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cytogfr.2016.03.002","article-title":"The emerging role of interferon regulatory factor 9 in the antiviral host response and beyond","volume":"29","author":"Suprunenko","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cytogfr.2016.02.010","article-title":"The unique role of STAT2 in constitutive and IFN-induced transcription and antiviral responses","volume":"29","author":"Blaszczyk","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6932","DOI":"10.1128\/JVI.07147-11","article-title":"Mice deficient in STAT1 but not STAT2 or IRF9 develop a lethal CD4+ T-cell-mediated disease following infection with lymphocytic choriomeningitis virus","volume":"86","author":"Hofer","year":"2012","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1126\/science.1235208","article-title":"Blockade of chronic type I interferon signaling to control persistent LCMV infection","volume":"340","author":"Wilson","year":"2013","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.1128\/jvi.69.8.4792-4796.1995","article-title":"Antiviral defense in mice lacking both alpha\/beta and gamma interferon receptors","volume":"69","author":"Huang","year":"1995","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e01219-17","DOI":"10.1128\/JVI.01219-17","article-title":"IRF9 Prevents CD8(+) T Cell Exhaustion in an Extrinsic Manner during Acute Lymphocytic Choriomeningitis Virus Infection","volume":"91","author":"Huber","year":"2017","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"220","DOI":"10.4049\/jimmunol.153.1.220","article-title":"Altered tissue distribution of viral replication and T cell spreading is pivotal in the protection against fatal lymphocytic choriomeningitis in mice after neutralization of IFN-alpha\/beta","volume":"153","author":"Sandberg","year":"1994","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s12974-016-0748-7","article-title":"Fast type I interferon response protects astrocytes from flavivirus infection and virus-induced cytopathic effects","volume":"13","author":"Lindqvist","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.vetmic.2017.03.022","article-title":"Alpha\/beta interferon receptor deficiency in mice significantly enhances susceptibility of the animals to pseudorabies virus infection","volume":"203","author":"Wei","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"307ra154","DOI":"10.1126\/scitranslmed.aac4227","article-title":"Human IFNAR2 deficiency: Lessons for antiviral immunity","volume":"7","author":"Duncan","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"7514","DOI":"10.1128\/JVI.79.12.7514-7527.2005","article-title":"Differential regulation of interferon regulatory factor (IRF)-7 and IRF-9 gene expression in the central nervous system during viral infection","volume":"79","author":"Ousman","year":"2005","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1089\/vim.2011.0006","article-title":"Evaluation of the immunomodulatory and antiviral effects of the cytokine combination IFN-alpha and IL-7 in the lymphocytic choriomeningitis virus and Friend retrovirus mouse infection models","volume":"24","author":"Audige","year":"2011","journal-title":"Viral Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Sullivan, B.M., Teijaro, J.R., de la Torre, J.C., and Oldstone, M.B.A. (2015). Early virus-host interactions dictate the course of a persistent infection. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004588"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.coi.2015.03.002","article-title":"New insights into type I interferon and the immunopathogenesis of persistent viral infections","volume":"34","author":"Snell","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.it.2017.05.005","article-title":"Type I Interferon in Chronic Virus Infection and Cancer","volume":"38","author":"Snell","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S195","DOI":"10.1007\/s00277-015-2326-y","article-title":"The interferon-alpha revival in CML","volume":"94","author":"Talpaz","year":"2015","journal-title":"Ann. Hematol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1200\/JCO.2010.32.0598","article-title":"Tolerability-adapted imatinib 800 mg\/d versus 400 mg\/d versus 400 mg\/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia","volume":"29","author":"Hehlmann","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrc.2016.14","article-title":"Antitumour actions of interferons: implications for cancer therapy","volume":"16","author":"Parker","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.3390\/v2112443","article-title":"Inhibition of the type I interferon antiviral response during arenavirus infection","volume":"2","author":"Borrow","year":"2010","journal-title":"Viruses"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Lee, M.S., Park, C.H., Jeong, Y.H., Kim, Y.J., and Ha, S.J. (2013). Negative regulation of type I IFN expression by OASL1 permits chronic viral infection and CD8(+) T-cell exhaustion. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003478"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/ni.2535","article-title":"OASL1 inhibits translation of the type I interferon-regulating transcription factor IRF7","volume":"14","author":"Lee","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"641","DOI":"10.4049\/jimmunol.1202448","article-title":"The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection","volume":"190","author":"Cook","year":"2013","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.immuni.2014.05.004","article-title":"Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity","volume":"40","author":"Xu","year":"2014","journal-title":"Immunity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4525","DOI":"10.4049\/jimmunol.176.8.4525","article-title":"CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion","volume":"176","author":"Aichele","year":"2006","journal-title":"J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1084\/jem.20050821","article-title":"Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection","volume":"202","author":"Kolumam","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Keppler, S.J., Rosenits, K., Koegl, T., Vucikuja, S., and Aichele, P. (2012). Signal 3 cytokines as modulators of primary immune responses during infections: the interplay of type I IFN and IL-12 in CD8 T cell responses. PLoS One, 7.","DOI":"10.1371\/journal.pone.0040865"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1084\/jem.189.8.1315","article-title":"Two roads diverged: interferon alpha\/beta- and interleukin 12-mediated pathways in promoting T cell interferon gamma responses during viral infection","volume":"189","author":"Cousens","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_94","first-page":"7","article-title":"Innate immune responses to LCMV infections: natural killer cells and cytokines","volume":"263","author":"Biron","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1128\/jvi.62.6.2102-2106.1988","article-title":"T4+ T helper cell function in vivo: differential requirement for induction of antiviral cytotoxic T-cell and antibody responses","volume":"62","author":"Ahmed","year":"1988","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8056","DOI":"10.1128\/jvi.68.12.8056-8063.1994","article-title":"CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection","volume":"68","author":"Matloubian","year":"1994","journal-title":"J. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.4049\/jimmunol.176.6.3315","article-title":"Cutting Edge: The direct action of type I IFN on CD4 T cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection","volume":"176","author":"Kolumam","year":"2006","journal-title":"J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"21182","DOI":"10.1073\/pnas.1118450109","article-title":"Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection","volume":"108","author":"Aubert","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/imm.12771","article-title":"Regulation of CD4 T cells and their effects on immunopathological inflammation following viral infection","volume":"152","author":"Bhattacharyya","year":"2017","journal-title":"Immunology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1084\/jem.20131556","article-title":"Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection","volume":"211","author":"Srivastava","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.virol.2013.02.015","article-title":"Interferon regulatory factor 7 (IRF7) is required for the optimal initial control but not subsequent clearance of lymphocytic choriomeningitis virus infection in mice","volume":"439","author":"Li","year":"2013","journal-title":"Virology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"11254","DOI":"10.1128\/JVI.00576-12","article-title":"Role of interferon regulatory factor 7 in T cell responses during acute lymphocytic choriomeningitis virus infection","volume":"86","author":"Zhou","year":"2012","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nri1783","article-title":"Antiviral antibody responses: the two extremes of a wide spectrum","volume":"6","author":"Hangartner","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/eji.1830160807","article-title":"Immunity to lymphocytic choriomeningitis virus in B cell-depleted mice: evidence for B cell and antibody-independent protection by memory T cells","volume":"16","author":"Cerny","year":"1986","journal-title":"Eur. J. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Bergthaler, A., Flatz, L., Verschoor, A., Hegazy, A.N., Holdener, M., Fink, K., Eschli, B., Merkler, D., Sommerstein, R., and Horvath, E. (2009). Impaired antibody response causes persistence of prototypic T cell-contained virus. PLoS Biol., 7.","DOI":"10.1371\/annotation\/42dca769-eca8-4e8f-a6b5-236355b631ff"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/nm1670","article-title":"Extralymphatic virus sanctuaries as a consequence of potent T-cell activation","volume":"13","author":"Recher","year":"2007","journal-title":"Nat. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.4049\/jimmunol.171.9.4733","article-title":"Deficient CD4+ T cell priming and regression of CD8+ T cell functionality in virus-infected mice lacking a normal B cell compartment","volume":"171","author":"Christensen","year":"2003","journal-title":"J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"eaah3565","DOI":"10.1126\/sciimmunol.aah3565","article-title":"Type I interferon suppresses virus-specific B cell responses by modulating CD8(+) T cell differentiation","volume":"1","author":"Moseman","year":"2016","journal-title":"Sci. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3389\/fimmu.2016.00564","article-title":"Type I Interferon Impairs Specific Antibody Responses Early during Establishment of LCMV Infection","volume":"7","author":"Daugan","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1128\/JVI.01640-07","article-title":"Lymphocytoid choriomeningitis virus activates plasmacytoid dendritic cells and induces a cytotoxic T-cell response via MyD88","volume":"82","author":"Jung","year":"2008","journal-title":"J. Virol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1073\/pnas.1117359109","article-title":"Plasmacytoid dendritic cells control T-cell response to chronic viral infection","volume":"109","author":"Lewis","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.4049\/jimmunol.181.6.3804","article-title":"MyD88 plays a critical T cell-intrinsic role in supporting CD8 T cell expansion during acute lymphocytic choriomeningitis virus infection","volume":"181","author":"Rahman","year":"2008","journal-title":"J. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"7384","DOI":"10.1128\/JVI.07090-11","article-title":"Differential impact of interferon regulatory factor 7 in initiation of the type I interferon response in the lymphocytic choriomeningitis virus-infected central nervous system versus the periphery","volume":"86","author":"Christensen","year":"2012","journal-title":"J. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1182\/blood-2007-10-117861","article-title":"Hematopoietic cell-derived interferon controls viral replication and virus-induced disease","volume":"113","author":"Lang","year":"2009","journal-title":"Blood"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1084\/jem.20070401","article-title":"High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells","volume":"204","author":"Miyagi","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"7578","DOI":"10.1128\/JVI.03117-13","article-title":"IRF7-dependent type I interferon production induces lethal immune-mediated disease in STAT1 knockout mice infected with lymphocytic choriomeningitis virus","volume":"88","author":"Li","year":"2014","journal-title":"J. Virol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e00437-16","DOI":"10.1128\/mBio.00437-16","article-title":"The Type I Interferon Response Determines Differences in Choroid Plexus Susceptibility between Newborns and Adults in Herpes Simplex Virus Encephalitis","volume":"7","author":"Wilcox","year":"2016","journal-title":"mBio"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.immuni.2005.01.005","article-title":"Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling","volume":"22","author":"Hahm","year":"2005","journal-title":"Immunity"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1101\/gad.4.10.1753","article-title":"Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator","volume":"4","author":"Kessler","year":"1990","journal-title":"Genes Dev."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1073\/pnas.92.9.3829","article-title":"Tyrosine-Phosphorylated Stat1 and Stat2 Plus a 48-kDa Protein All Contact DNA in Forming Interferon-Stimulated-Gene Factor 3","volume":"92","author":"Qureshi","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","first-page":"196","article-title":"Two domains of ISGF3 gamma that mediate protein-DNA and protein-protein interactions during transcription factor assembly contribute to DNA-binding specificity","volume":"13","author":"Veals","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1046\/j.1365-2443.1996.870287.x","article-title":"Regulation of IFN-alpha\/beta genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha\/beta","volume":"1","author":"Harada","year":"1996","journal-title":"Genes Cells"},{"key":"ref_123","first-page":"4189","article-title":"Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons","volume":"11","author":"John","year":"1991","journal-title":"Mol. Cell. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1046\/j.1365-2443.1996.08008.x","article-title":"Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies","volume":"1","author":"Kimura","year":"1996","journal-title":"Genes Cells"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/2\/172\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:33:28Z","timestamp":1760186008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/2\/172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,20]]},"references-count":124,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["v11020172"],"URL":"https:\/\/doi.org\/10.3390\/v11020172","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,20]]}}}