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Elsevier Ltd"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"278","DOI":"10.2307\/4595031","article-title":"Venezuelan equine encephalitis epidemic in Texas, 1971","volume":"89","author":"RB Zehmer","year":"1974","journal-title":"Health Serv Rep"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"58","DOI":"10.7774\/cevr.2014.3.1.58","article-title":"Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses","volume":"3","author":"YY Go","year":"2014","journal-title":"Clin Exp Vaccine Res"},{"key":"ref46","article-title":"A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease","author":"T Couderc","year":"2008","journal-title":"PLoS Pathog"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1128\/JVI.74.11.5006-5015.2000","article-title":"Pegylated alpha interferon is an effective treatment for virulent venezuelan equine encephalitis virus and has profound effects on the host immune response to infection","volume":"74","author":"RA Lukaszewski","year":"2000","journal-title":"Journal of Virology"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1089\/jir.1990.10.293","article-title":"Comparative therapeutic efficacy of recombinant interferons-alpha, -beta, and -gamma against alphatogavirus, bunyavirus, flavivirus, and herpesvirus infections","volume":"10","author":"AJ Pinto","year":"1990","journal-title":"J Interferon Res"},{"key":"ref49","first-page":"606","article-title":"Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff","volume":"85","author":"LK White","year":"2011","journal-title":"Journal of Virology. 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Portland Press Ltd"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.4049\/jimmunol.177.7.4530","article-title":"STAT1-independent cell type-specific regulation of antiviral APOBEC3G by IFN-alpha","volume":"177","author":"PTN Sarkis","year":"2006","journal-title":"The Journal of Immunology"},{"key":"ref86","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":"B Hahm","year":"2005","journal-title":"Immunity"},{"key":"ref87","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":"SS Ousman","year":"2005","journal-title":"Journal of Virology"},{"key":"ref88","first-page":"1517","article-title":"Interferon-inducible protein 10 induction and inhibition of angiogenesis in vivo by the antitumor agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA)","volume":"61","author":"Z Cao","year":"2001","journal-title":"Cancer Res"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"e60038","DOI":"10.1371\/journal.pone.0060038","article-title":"The Chemotherapeutic Agent DMXAA as a Unique IRF3-Dependent Type-2 Vaccine Adjuvant","volume":"8","author":"CK Tang","year":"2013","journal-title":"PLoS ONE"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1128\/AAC.04321-14","article-title":"STING Agonists Induce an Innate Antiviral Immune Response against Hepatitis B Virus","volume":"59","author":"F Guo","year":"2015","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"133","DOI":"10.4269\/ajtmh.2008.79.133","article-title":"An animal model for studying the pathogenesis of chikungunya virus infection","volume":"79","author":"SA Ziegler","year":"2008","journal-title":"Am J Trop Med Hyg"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"8021","DOI":"10.1128\/JVI.02603-09","article-title":"Chikungunya Virus Arthritis in Adult Wild-Type Mice","volume":"84","author":"J Gardner","year":"2010","journal-title":"Journal of Virology"},{"key":"ref93","first-page":"32","article-title":"A Mouse Model of Chikungunya Virus\u2014Induced Musculoskeletal Inflammatory Disease","volume":"178","author":"TE Morrison","year":"2011","journal-title":"AJPA. Elsevier Inc"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"13878","DOI":"10.1128\/JVI.02666-13","article-title":"Chronic joint disease caused by persistent Chikungunya virus infection is controlled by the adaptive immune response","volume":"87","author":"DW Hawman","year":"2013","journal-title":"Journal of Virology"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/infdis\/142.3.394","article-title":"Protection against Japanese encephalitis virus in mice and hamsters by treatment with carboxymethylacridanone, a potent interferon inducer","volume":"142","author":"JL Taylor","year":"1980","journal-title":"J Infect Dis. Oxford University Press"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/2051013613501988","article-title":"Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants","volume":"1","author":"TW Dubensky","year":"2013","journal-title":"Ther Adv Vaccines"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1126\/science.1244040","article-title":"Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects. 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BioMed Central Ltd"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1038\/sj.bjc.6600368","article-title":"Induction of endothelial cell apoptosis by the antivascular agent 5,6-Dimethylxanthenone-4-acetic acid","volume":"86","author":"LM Ching","year":"2002","journal-title":"British Journal of Cancer"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0360-3016(02)03920-2","article-title":"DMXAA: an antivascular agent with multiple host responses","volume":"54","author":"BC Baguley","year":"2002","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1600-065X.2012.01099.x","article-title":"NF-\u03baB and the link between inflammation and cancer","volume":"246","author":"JA DiDonato","year":"2012","journal-title":"Immunol Rev"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.tcb.2012.08.001","article-title":"The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation","volume":"22","author":"L Tornatore","year":"2012","journal-title":"Trends in Cell Biology"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1002\/emmm.201201650","article-title":"Defining critical roles for NF-\u03baB p65 and type I interferon in innate immunity to rhinovirus","volume":"4","author":"NW Bartlett","year":"2012","journal-title":"EMBO Mol Med"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"4814","DOI":"10.1128\/MCB.20.13.4814-4825.2000","article-title":"Assembly of a Functional Beta Interferon Enhanceosome Is Dependent on ATF-2-c-jun Heterodimer Orientation","volume":"20","author":"JV Falvo","year":"2000","journal-title":"Mol Cell Biol"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.4049\/jimmunol.1000114","article-title":"NF- B RelA Subunit Is Crucial for Early IFN- Expression and Resistance to RNA Virus Replication","volume":"185","author":"J Wang","year":"2010","journal-title":"The Journal of Immunology"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.cell.2007.05.019","article-title":"An atomic model of the interferon-beta enhanceosome","volume":"129","author":"D Panne","year":"2007","journal-title":"Cell"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.4049\/jimmunol.1202749","article-title":"Proteasomal Degradation of Herpes Simplex Virus Capsids in Macrophages Releases DNA to the Cytosol for Recognition by DNA Sensors","volume":"190","author":"KA Horan","year":"2013","journal-title":"The Journal of Immunology"},{"key":"ref109","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","author":"CA Lipinski","year":"2012","journal-title":"Advanced Drug Delivery Reviews. Elsevier"},{"key":"ref110","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","volume":"22","author":"B Hahm","year":"2005","journal-title":"Signaling. Immunity"},{"key":"ref111","first-page":"7514","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":"SS Ousman","year":"2005","journal-title":"Journal of Virology. American Society for Microbiology"},{"key":"ref112","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1089\/jir.2005.25.733","article-title":"Stats: multifaceted regulators of transcription","volume":"25","author":"MM Brierley","year":"2005","journal-title":"Journal of Interferon & Cytokine Research"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"5255","DOI":"10.4049\/jimmunol.171.10.5255","article-title":"Differential responses to IFN-alpha subtypes in human T cells and dendritic cells","volume":"171","author":"CMU Hilkens","year":"2003","journal-title":"The Journal of Immunology"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cyto.2010.09.006","article-title":"The differential activity of interferon-\u03b1 subtypes is consistent among distinct target genes and cell types","volume":"53","author":"HP Moll","year":"2011","journal-title":"Cytokine"},{"key":"ref115","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/eji.201444747","article-title":"Dendritic cell specific targeting of MyD88 signalling pathways in vivo","volume":"45","author":"C Arnold-Schrauf","year":"2015","journal-title":"Eur J Immunol"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/978-1-61779-340-0_15","article-title":"Evaluation of innate immune signaling pathways in transformed cells","volume":"797","author":"JF Heiber","year":"2012","journal-title":"Methods Mol Biol"},{"key":"ref117","doi-asserted-by":"crossref","first-page":"5914","DOI":"10.4049\/jimmunol.0900255","article-title":"Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response","volume":"184","author":"JJ Hoarau","year":"2010","journal-title":"The Journal of Immunology"},{"key":"ref118","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1182\/blood-2010-06-291245","article-title":"IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin","volume":"117","author":"S Botto","year":"2011","journal-title":"Blood"},{"key":"ref119","doi-asserted-by":"crossref","first-page":"11943","DOI":"10.1128\/JVI.79.18.11943-11951.2005","article-title":"The Src family kinase c-Yes is required for maturation of West Nile virus particles","volume":"79","author":"AJ Hirsch","year":"2005","journal-title":"Journal of Virology"},{"key":"ref120","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.chom.2009.09.013","article-title":"Cowpox virus inhibits the transporter associated with antigen processing to evade T cell recognition","volume":"6","author":"D Alzhanova","year":"2009","journal-title":"Cell Host and Microbe. 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