{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:03:58Z","timestamp":1791993838963,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T00:00:00Z","timestamp":1315353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV) and Marburgvirus (MARV), causes severe and often times lethal hemorrhagic fever in humans. Filoviral infections are associated with ineffective innate antiviral responses as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses. The Type I interferon (IFN) response is critical for establishing an antiviral state in the host cell and subsequent activation of the adaptive immune responses. Several filoviral encoded components target Type I IFN responses, and this innate immune suppression is important for viral replication and pathogenesis. For example, EBOV VP35 inhibits the phosphorylation of IRF-3\/7 by the TBK-1\/IKK\u03b5 kinases in addition to sequestering viral RNA from detection by RIG-I like receptors. MARV VP40 inhibits STAT1\/2 phosphorylation by inhibiting the JAK family kinases. EBOV VP24 inhibits nuclear translocation of activated STAT1 by karyopherin-\u03b1. The examples also represent distinct mechanisms utilized by filoviral proteins in order to counter immune responses, which results in limited IFN-\u03b1\/\u03b2 production and downstream signaling.<\/jats:p>","DOI":"10.3390\/v3091634","type":"journal-article","created":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T10:26:06Z","timestamp":1315391166000},"page":"1634-1649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Filoviral Immune Evasion Mechanisms"],"prefix":"10.3390","volume":"3","author":[{"given":"Parameshwaran","family":"Ramanan","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA"},{"name":"Biochemistry Graduate Program, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed S.","family":"Shabman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig S.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA"},{"name":"Biochemistry Undergraduate Program, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaya K.","family":"Amarasinghe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher F.","family":"Basler","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy W.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2011,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0168-1702(02)00087-4","article-title":"Molecular characterization of an isolate from the 1989\/90 epizootic of Ebola virus Reston among macaques imported into the United States","volume":"87","author":"Groseth","year":"2002","journal-title":"Virus Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/0140-6736(90)90737-P","article-title":"Preliminary report: Isolation of Ebola virus from monkeys imported to USA","volume":"335","author":"Jahrling","year":"1990","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1126\/science.1172705","article-title":"Discovery of swine as a host for the Reston ebolavirus","volume":"325","author":"Barrette","year":"2009","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/438575a","article-title":"Fruit bats as reservoirs of Ebola virus","volume":"438","author":"Leroy","year":"2005","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Towner, J.S., Pourrut, X., Albarino, C.G., Nkogue, C.N., Bird, B.H., Grard, G., Ksiazek, T.G., Gonzalez, J.P., Nichol, S.T., and Leroy, E.M. (2007). Marburg virus infection detected in a common African bat. PLoS One, 2.","DOI":"10.1371\/journal.pone.0000764"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Towner, J.S., Amman, B.R., Sealy, T.K., Carroll, S.A., Comer, J.A., Kemp, A., Swanepoel, R., Paddock, C.D., Balinandi, S., and Khristova, M.L. (2009). Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000536"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1099\/0022-1317-82-6-1365","article-title":"The role of the Type I interferon response in the resistance of mice to filovirus infection","volume":"82","author":"Bray","year":"2001","journal-title":"J. Gen. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(10)60667-8","article-title":"Ebola haemorrhagic fever","volume":"377","author":"Feldmann","year":"2011","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1600-065X.2008.00737.x","article-title":"Innate immunity to virus infection","volume":"227","author":"Takeuchi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1600-065X.2008.00727.x","article-title":"RNA recognition and signal transduction by RIG-I-like receptors","volume":"227","author":"Yoneyama","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nri888","article-title":"Viruses and interferon: A fight for supremacy","volume":"2","author":"Katze","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5348","DOI":"10.1128\/JVI.00215-08","article-title":"Whole-genome expression profiling reveals that inhibition of host innate immune response pathways by Ebola virus can be reversed by a single amino acid change in the VP35 protein","volume":"82","author":"Hartman","year":"2008","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1128\/JVI.80.6.3009-3020.2006","article-title":"Global suppression of the host antiviral response by Ebola- and Marburgviruses: Increased antagonism of the type I interferon response is associated with enhanced virulence","volume":"80","author":"Kash","year":"2006","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1128\/JVI.02190-10","article-title":"A new ebola virus nonstructural glycoprotein expressed through RNA editing","volume":"85","author":"Mehedi","year":"2011","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7945","DOI":"10.1128\/JVI.77.14.7945-7956.2003","article-title":"The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3","volume":"77","author":"Basler","year":"2003","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12289","DOI":"10.1073\/pnas.220398297","article-title":"The Ebola virus VP35 protein functions as a type I IFN antagonist","volume":"97","author":"Basler","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5168","DOI":"10.1128\/JVI.02199-05","article-title":"Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha\/beta interferon production induced by RIG-I signaling","volume":"80","author":"Cardenas","year":"2006","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.virol.2004.07.006","article-title":"A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for type I interferon antagonism and displays high identity with the RNA-binding domain of another interferon antagonist, the NS1 protein of influenza A virus","volume":"328","author":"Hartman","year":"2004","journal-title":"Virology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6430","DOI":"10.1128\/JVI.00044-06","article-title":"Reverse genetic generation of recombinant Zaire Ebola viruses containing disrupted IRF-3 inhibitory domains results in attenuated virus growth in vitro and higher levels of IRF-3 activation without inhibiting viral transcription or replication","volume":"80","author":"Hartman","year":"2006","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1073\/pnas.0807854106","article-title":"Structure of the Ebola VP35 interferon inhibitory domain","volume":"106","author":"Leung","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nsmb.1765","article-title":"Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35","volume":"17","author":"Leung","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1128\/JVI.02459-09","article-title":"Mutations abrogating VP35 interaction with double-stranded RNA render Ebola virus avirulent in guinea pigs","volume":"84","author":"Prins","year":"2010","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.virol.2005.06.044","article-title":"Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein","volume":"341","author":"Reid","year":"2005","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1128\/JVI.01875-08","article-title":"Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1","volume":"83","author":"Prins","year":"2009","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chang, T.H., Kubota, T., Matsuoka, M., Jones, S., Bradfute, S.B., Bray, M., and Ozato, K. (2009). Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000493"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1128\/JVI.01006-06","article-title":"The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR","volume":"81","author":"Feng","year":"2007","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8993","DOI":"10.1128\/JVI.00523-09","article-title":"Ebola virus VP35 antagonizes PKR activity through its C-terminal interferon inhibitory domain","volume":"83","author":"Schumann","year":"2009","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Haasnoot, J., de Vries, W., Geutjes, E.J., Prins, M., de Haan, P., and Berkhout, B. (2007). The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030086"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1128\/JVI.01160-10","article-title":"Ebolavirus proteins suppress the effects of small interfering RNA by direct interaction with the mammalian RNA interference pathway","volume":"85","author":"Fabozzi","year":"2011","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1073\/pnas.0910547107","article-title":"Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression","volume":"107","author":"Kimberlin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jmb.2010.04.022","article-title":"Structural and Functional Characterization of Reston Ebola Virus VP35 Interferon Inhibitory Domain","volume":"399","author":"Leung","year":"2010","journal-title":"J. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13469","DOI":"10.1128\/JVI.01097-07","article-title":"Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1","volume":"81","author":"Reid","year":"2007","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0042-6822(85)90236-3","article-title":"Descriptive analysis of Ebola virus proteins","volume":"147","author":"Elliott","year":"1985","journal-title":"Virology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7344","DOI":"10.1128\/JVI.78.14.7344-7351.2004","article-title":"Contribution of ebola virus glycoprotein, nucleoprotein, and VP24 to budding of VP40 virus-like particles","volume":"78","author":"Licata","year":"2004","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7260","DOI":"10.1128\/JVI.00051-06","article-title":"Infection of naive target cells with virus-like particles: implications for the function of ebola virus VP24","volume":"80","author":"Hoenen","year":"2006","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.virol.2010.04.002","article-title":"Both matrix proteins of Ebola virus contribute to the regulation of viral genome replication and transcription","volume":"403","author":"Hoenen","year":"2010","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S1097-2765(02)00588-9","article-title":"The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein","volume":"10","author":"Huang","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S247","DOI":"10.1086\/520596","article-title":"Regions in Ebola virus VP24 that are important for nucleocapsid formation","volume":"196","author":"Noda","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S284","DOI":"10.1086\/520582","article-title":"Ebola virus (EBOV) VP24 inhibits transcription and replication of the EBOV genome","volume":"196","author":"Watanabe","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S248","DOI":"10.1086\/514292","article-title":"A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever","volume":"179","author":"Bray","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ebihara, H., Takada, A., Kobasa, D., Jones, S., Neumann, G., Theriault, S., Bray, M., Feldmann, H., and Kawaoka, Y. (2006). Molecular determinants of Ebola virus virulence in mice. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020073"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1006\/viro.2000.0572","article-title":"Molecular characterization of guinea pig-adapted variants of Ebola virus","volume":"277","author":"Volchkov","year":"2000","journal-title":"Virology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1128\/JVI.01372-09","article-title":"Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling","volume":"84","author":"Mateo","year":"2010","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5156","DOI":"10.1128\/JVI.02349-05","article-title":"Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation","volume":"80","author":"Reid","year":"2006","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1600-0854.2005.00263.x","article-title":"An unconventional NLS is critical for the nuclear import of the influenza A virus nucleoprotein and ribonucleoprotein","volume":"6","author":"Cros","year":"2005","journal-title":"Traffic"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/S0042-6822(95)80026-3","article-title":"NPI-1, the human homolog of SRP-1, interacts with influenza virus nucleoprotein","volume":"206","author":"Palese","year":"1995","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"27981","DOI":"10.1074\/jbc.M303275200","article-title":"Structural basis for the specificity of bipartite nuclear localization sequence binding by importin-alpha","volume":"278","author":"Fontes","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jsb.2009.05.001","article-title":"Fold prediction of VP24 protein of Ebola and Marburg viruses using de novo fragment assembly","volume":"167","author":"Lee","year":"2009","journal-title":"J. Struct. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1128\/JVI.02429-08","article-title":"The marburg virus 3' noncoding region structurally and functionally differs from that of ebola virus","volume":"83","author":"Enterlein","year":"2009","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Valmas, C., Grosch, M.N., Schumann, M., Olejnik, J., Martinez, O., Best, S.M., Krahling, V., Basler, C.F., and Muhlberger, E. (2010). Marburg virus evades interferon responses by a mechanism distinct from ebola virus. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000721"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.1093\/emboj\/19.16.4228","article-title":"Crystal structure of the matrix protein VP40 from Ebola virus","volume":"19","author":"Dessen","year":"2000","journal-title":"EMBO J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0969-2126(03)00050-9","article-title":"The matrix protein VP40 from Ebola virus octamerizes into pore-like structures with specific RNA binding properties","volume":"11","author":"Dessen","year":"2003","journal-title":"Structure"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1006\/jmbi.2000.3822","article-title":"Structural characterization and membrane binding properties of the matrix protein VP40 of Ebola virus","volume":"300","author":"Ruigrok","year":"2000","journal-title":"J. Mol. Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/3\/9\/1634\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:57:19Z","timestamp":1760219839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/3\/9\/1634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,7]]},"references-count":53,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2011,9]]}},"alternative-id":["v3091634"],"URL":"https:\/\/doi.org\/10.3390\/v3091634","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9,7]]}}}