{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T21:17:53Z","timestamp":1778707073400,"version":"3.51.4"},"reference-count":163,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Alphaviruses are arboviruses that cause arthritis and encephalitis in humans. Eastern Equine Encephalitis Virus (EEEV) is a mosquito-transmitted alphavirus that is implicated in severe encephalitis in humans with high mortality. However, limited insights are available into the fundamental biology of EEEV and residue-level details of its interactions with host proteins. In recent years, outbreaks of EEEV have been reported mainly in the United States, raising concerns about public safety. This review article summarizes recent advances in the structural biology of EEEV based mainly on single-particle cryogenic electron microscopy (cryoEM) structures. Together with functional analyses of EEEV and related alphaviruses, these structural investigations provide clues to how EEEV interacts with host proteins, which may open avenues for the development of therapeutics.<\/jats:p>","DOI":"10.3390\/pathogens10080973","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:44:32Z","timestamp":1627854272000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Structural Biology of Eastern Equine Encephalitis Virus, an Emerging Viral Threat"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0759-7511","authenticated-orcid":false,"given":"S. Saif","family":"Hasan","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201, USA"},{"name":"Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 9600 Gudelsky Drive, Rockville, MD 20850, USA"},{"name":"University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical Center, 22. S. Greene St., Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debajit","family":"Dey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suruchi","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/mr.58.3.491-562.1994","article-title":"The alphaviruses: Gene expression, replication, and evolution","volume":"58","author":"Strauss","year":"1994","journal-title":"Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nrrheum.2012.64","article-title":"Arthritogenic alphaviruses\u2014An overview","volume":"8","author":"Suhrbier","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Levi, L.I., and Vignuzzi, M. (2019). Arthritogenic alphaviruses: A worldwide emerging threat?. Microorganisms, 7.","DOI":"10.3390\/microorganisms7050133"},{"key":"ref_4","first-page":"29853","article-title":"Global emergence of alphaviruses that cause arthritis in humans","volume":"5","author":"Lwande","year":"2015","journal-title":"Infect. Ecol. Epidemiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1196\/annals.1408.007","article-title":"The molecular and cellular aspects of arthritis due to alphavirus infections: Lesson learned from Ross River virus","volume":"1102","author":"Rulli","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.vetmic.2009.08.023","article-title":"Encephalitic alphaviruses","volume":"140","author":"Zacks","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1126\/science.78.2034.587.b","article-title":"The immunological relationship of Eastern and Western strains of Equine encephalomyelitis virus","volume":"78","author":"Giltner","year":"1933","journal-title":"Science"},{"key":"ref_8","unstructured":"WHO (2006). Outbreak news. Chikungunya and dengue, south-west Indian Ocean. Wkly. Epidemiol. Rec., 81, 106\u2013108."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1056\/NEJMp1213696","article-title":"Eastern equine encephalitis virus-Old enemy, new threat","volume":"368","author":"Armstrong","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1056\/NEJM194906162402403","article-title":"The sequelae of Eastern equine encephalomyelitis","volume":"240","author":"Ayres","year":"1949","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.4269\/ajtmh.17-0927","article-title":"Eastern equine encephalitis virus in the United States, 2003\u20132016","volume":"98","author":"Lindsey","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"50","DOI":"10.15585\/mmwr.mm6902a4","article-title":"Notes from the field: Multistate outbreak of Eastern equine encephalitis virus-United States, 2019","volume":"69","author":"Lindsey","year":"2020","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1093\/jmedent\/35.3.296","article-title":"Multiple isolations of Eastern equine encephalitis and highlands J viruses from mosquitoes (Diptera: Culicidae) during a 1996 epizootic in southeastern Connecticut","volume":"35","author":"Andreadis","year":"1998","journal-title":"J. Med. Entomol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1080\/22221751.2020.1774426","article-title":"Spatial and temporal expansions of Eastern equine encephalitis virus and phylogenetic groups isolated from mosquitoes and mammalian cases in New York State from 2013 to 2019","volume":"9","author":"Oliver","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3201\/eid1902.120039","article-title":"Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970\u20132010","volume":"19","author":"Silverman","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","unstructured":"CDC (2021, June 01). Eastern Equine Encephalitis (EEE), Available online: https:\/\/www.cdc.gov\/easternequineencephalitis\/tech\/epi.html."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1056\/NEJMp1914328","article-title":"Eastern equine encephalitis virus-Another emergent arbovirus in the United States","volume":"381","author":"Morens","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1017\/S0950268820000308","article-title":"Cases of Eastern equine encephalitis in humans associated with Aedes canadensis, Coquillettidia perturbans and Culiseta melanura mosquitoes with the virus in New York State from 1971 to 2012 by analysis of aggregated published data","volume":"148","author":"Sherwood","year":"2020","journal-title":"Epidemiol. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"250","DOI":"10.4269\/ajtmh.1991.44.250","article-title":"Detection of Eastern equine encephalomyelitis virus deposition in Culiseta melanura following ingestion of radiolabeled virus in blood meals","volume":"44","author":"Weaver","year":"1991","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1126\/science.1321985","article-title":"Isolation of Eastern equine encephalitis virus from Aedes albopictus in Florida","volume":"257","author":"Mitchell","year":"1992","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"959","DOI":"10.3389\/fmicb.2016.00959","article-title":"Neurological sequelae resulting from encephalitic alphavirus infection","volume":"7","author":"Ronca","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.jcv.2008.03.008","article-title":"Eastern equine encephalitis leading to multi-organ failure and sepsis","volume":"42","author":"Reddy","year":"2008","journal-title":"J. Clin. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1056\/NEJMoa1212628","article-title":"Eastern equine encephalitis in Latin America","volume":"369","author":"Carrera","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0166-3542(02)00203-6","article-title":"Viruses of the Bunya- and Togaviridae families: Potential as bioterrorism agents and means of control","volume":"57","author":"Sidwell","year":"2003","journal-title":"Antiviral Res."},{"key":"ref_25","unstructured":"CDC-USDA (2021, June 01). HHS and USDA Select Agents and Toxins, Available online: https:\/\/www.selectagents.gov\/sat\/list.htm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1089\/bsp.2009.0032","article-title":"Alphavirus antiviral drug development: Scientific gap analysis and prospective research areas","volume":"7","author":"Reichert","year":"2009","journal-title":"Biosecur. Bioterror"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Trobaugh, D.W., Sun, C., Dunn, M.D., Reed, D.S., and Klimstra, W.B. (2019). Rational design of a live-attenuated Eastern equine encephalitis virus vaccine through informed mutation of virulence determinants. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007584"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/0042-6822(84)90428-8","article-title":"Complete nucleotide sequence of the genomic RNA of Sindbis virus","volume":"133","author":"Strauss","year":"1984","journal-title":"Virology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0042-6822(88)90292-9","article-title":"Genome sequences of a mouse-avirulent and a mouse-virulent strain of Ross River virus","volume":"163","author":"Faragher","year":"1988","journal-title":"Virology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/288236a0","article-title":"Nucleotide sequence of cDNA coding for Semliki Forest virus membrane glycoproteins","volume":"288","author":"Garoff","year":"1980","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1099\/0022-1317-68-8-2129","article-title":"Nucleotide sequence of the genome region encoding the 26S mRNA of Eastern equine encephalomyelitis virus and the deduced amino acid sequence of the viral structural proteins","volume":"68 Pt 8","author":"Chang","year":"1987","journal-title":"J. Gen. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1146\/annurev.mi.42.100188.003301","article-title":"Evolution of RNA viruses","volume":"42","author":"Strauss","year":"1988","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1016\/j.celrep.2018.11.067","article-title":"Cryo-EM structures of Eastern equine encephalitis virus reveal mechanisms of virus disassembly and antibody neutralization","volume":"25","author":"Hasan","year":"2018","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"249640","DOI":"10.1155\/2011\/249640","article-title":"Replication of alphaviruses: A review on the entry process of alphaviruses into cells","volume":"2011","author":"Leung","year":"2011","journal-title":"Adv. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2217\/fmb.09.59","article-title":"A structural and functional perspective of alphavirus replication and assembly","volume":"4","author":"Jose","year":"2009","journal-title":"Future Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41564-018-0286-4","article-title":"Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein","volume":"4","author":"Kim","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s41586-018-0121-3","article-title":"Mxra8 is a receptor for multiple arthritogenic alphaviruses","volume":"557","author":"Zhang","year":"2018","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ko, S.Y., Akahata, W., Yang, E.S., Kong, W.P., Burke, C.W., Honnold, S.P., Nichols, D.K., Huang, Y.S., Schieber, G.L., and Carlton, K. (2019). A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates. Sci. Transl. Med., 11.","DOI":"10.1126\/scitranslmed.aav3113"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1016\/j.cell.2020.11.011","article-title":"Human antibodies protect against aerosolized Eastern equine encephalitis virus infection","volume":"183","author":"Williamson","year":"2020","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9327","DOI":"10.1128\/JVI.05015-11","article-title":"The structure of Barmah Forest virus as revealed by cryo-electron microscopy at a 6\u00c5 resolution has detailed transmembrane protein architecture and interactions","volume":"85","author":"Kostyuchenko","year":"2011","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1097-2765(00)80421-9","article-title":"Cryo-electron microscopy reveals the functional organization of an enveloped virus, Semliki Forest virus","volume":"5","author":"Mancini","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.str.2005.07.025","article-title":"Mapping the structure and function of the E1 and E2 glycoproteins in alphaviruses","volume":"14","author":"Mukhopadhyay","year":"2006","journal-title":"Structure"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9775","DOI":"10.1128\/JVI.00876-10","article-title":"Structure of the recombinant alphavirus Western equine encephalitis virus revealed by cryoelectron microscopy","volume":"84","author":"Sherman","year":"2010","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10648","DOI":"10.1073\/pnas.92.23.10648","article-title":"Putative receptor binding sites on alphaviruses as visualized by cryoelectron microscopy","volume":"92","author":"Smith","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e00435","DOI":"10.7554\/eLife.00435","article-title":"Structural analyses at pseudo atomic resolution of Chikungunya virus and antibodies show mechanisms of neutralization","volume":"2","author":"Sun","year":"2013","journal-title":"eLife"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11645","DOI":"10.1128\/JVI.76.22.11645-11658.2002","article-title":"Placement of the structural proteins in Sindbis virus","volume":"76","author":"Zhang","year":"2002","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.virol.2004.11.043","article-title":"Heparin binding sites on Ross River virus revealed by electron cryo-microscopy","volume":"332","author":"Zhang","year":"2005","journal-title":"Virology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1038\/emboj.2011.261","article-title":"4.4 \u00c5 cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus","volume":"30","author":"Zhang","year":"2011","journal-title":"EMBO J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1038\/s41467-021-23400-9","article-title":"Cryo-EM structure of the mature and infective Mayaro virus at 4.4 \u00c5 resolution reveals features of arthritogenic alphaviruses","volume":"12","author":"Coimbra","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/0092-8674(95)90516-2","article-title":"Nucleocapsid and glycoprotein organization in an enveloped virus","volume":"80","author":"Cheng","year":"1995","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5081","DOI":"10.1093\/emboj\/19.19.5081","article-title":"Membrane proteins organize a symmetrical virus","volume":"19","author":"Forsell","year":"2000","journal-title":"EMBO J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/354037a0","article-title":"Structure of Sindbis virus core protein reveals a chymotrypsin-like serine proteinase and the organization of the virion","volume":"354","author":"Choi","year":"1991","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nature02239","article-title":"Conformational change and protein-protein interactions of the fusion protein of Semliki Forest virus","volume":"427","author":"Gibbons","year":"2004","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0092-8674(01)00303-8","article-title":"The fusion glycoprotein shell of Semliki Forest virus: An icosahedral assembly primed for fusogenic activation at endosomal pH","volume":"105","author":"Lescar","year":"2001","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nature09546","article-title":"Structural changes of envelope proteins during alphavirus fusion","volume":"468","author":"Li","year":"2010","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nature09555","article-title":"Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography","volume":"468","author":"Voss","year":"2010","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1093\/emboj\/cdf442","article-title":"Acid-induced movements in the glycoprotein shell of an alphavirus turn the spikes into membrane fusion mode","volume":"21","author":"Haag","year":"2002","journal-title":"EMBO J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7309","DOI":"10.1128\/jvi.66.12.7309-7318.1992","article-title":"Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein","volume":"66","author":"Wahlberg","year":"1992","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7349","DOI":"10.1128\/JVI.72.9.7349-7356.1998","article-title":"Binding of Sindbis virus to cell surface heparan sulfate","volume":"72","author":"Byrnes","year":"1998","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7357","DOI":"10.1128\/JVI.72.9.7357-7366.1998","article-title":"Adaptation of Sindbis virus to BHK cells selects for use of heparan sulfate as an attachment receptor","volume":"72","author":"Klimstra","year":"1998","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0042-6822(88)90141-9","article-title":"Semliki Forest virus particles containing only the E1 envelope glycoprotein are infectious and can induce cell-cell fusion","volume":"166","author":"Omar","year":"1988","journal-title":"Virology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1083\/jcb.116.2.339","article-title":"Membrane fusion process of Semliki Forest virus. I: Low pH-induced rearrangement in spike protein quaternary structure precedes virus penetration into cells","volume":"116","author":"Wahlberg","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5644","DOI":"10.1128\/JVI.00130-11","article-title":"Activation of the alphavirus spike protein is suppressed by bound E3","volume":"85","author":"Sjoberg","year":"2011","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"12261","DOI":"10.1016\/S0021-9258(19)86303-2","article-title":"Absence of a cleavable signal sequence in Sindbis virus glycoprotein PE2","volume":"254","author":"Bonatti","year":"1979","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1432-1033.1984.tb08130.x","article-title":"Role of signal recognition particle in the membrane assembly of Sindbis viral glycoproteins","volume":"140","author":"Bonatti","year":"1984","journal-title":"Eur. J. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/1743-422X-5-108","article-title":"Discovery of frameshifting in alphavirus 6K resolves a 20-year enigma","volume":"5","author":"Firth","year":"2008","journal-title":"Virol. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/jvi.65.1.147-154.1991","article-title":"Internally located cleavable signal sequences direct the formation of Semliki Forest virus membrane proteins from a polyprotein precursor","volume":"65","author":"Liljestrom","year":"1991","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1074\/jbc.M609125200","article-title":"The dynamic envelope of a fusion class II virus. Prefusion stages of Semliki Forest virus revealed by electron cryomicroscopy","volume":"282","author":"Wu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13362","DOI":"10.1073\/pnas.1301911110","article-title":"Characterization of an early-stage fusion intermediate of Sindbis virus using cryoelectron microscopy","volume":"110","author":"Cao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.virol.2004.03.046","article-title":"Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion","volume":"324","author":"Paredes","year":"2004","journal-title":"Virology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6940","DOI":"10.1128\/jvi.68.11.6940-6946.1994","article-title":"Membrane and protein interactions of a soluble form of the Semliki Forest virus fusion protein","volume":"68","author":"Klimjack","year":"1994","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0092-8674(03)00683-4","article-title":"Visualization of the target-membrane-inserted fusion protein of Semliki Forest virus by combined electron microscopy and crystallography","volume":"114","author":"Gibbons","year":"2003","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1128\/JVI.03310-12","article-title":"A key interaction between the alphavirus envelope proteins responsible for initial dimer dissociation during fusion","volume":"87","author":"Fields","year":"2013","journal-title":"J. Virol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4670","DOI":"10.1128\/JVI.02646-08","article-title":"Role of conserved histidine residues in the low-pH dependence of the Semliki Forest virus fusion protein","volume":"83","author":"Qin","year":"2009","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Sahoo, B., Gudigamolla, N.K., and Chowdary, T.K. (2020). Acidic pH-induced conformational changes in Chikungunya virus fusion protein E1: A spring-twisted region in the domain I\u2013III linker acts as a hinge point for swiveling motion of domains. J. Virol., 94.","DOI":"10.1128\/JVI.01561-20"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6334","DOI":"10.1128\/JVI.00596-11","article-title":"The domain I-domain III linker plays an important role in the fusogenic conformational change of the alphavirus membrane fusion protein","volume":"85","author":"Zheng","year":"2011","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.3390\/v7072792","article-title":"Early events in Chikungunya virus infection-From virus cell binding to membrane fusion","volume":"7","author":"Hoornweg","year":"2015","journal-title":"Viruses"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.virol.2007.07.012","article-title":"Venezuelan equine encephalitis virus infection of mosquito cells requires acidification as well as mosquito homologs of the endocytic proteins Rab5 and Rab7","volume":"369","author":"Colpitts","year":"2007","journal-title":"Virology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/0092-8674(83)90078-8","article-title":"Penetration of Semliki Forest virus from acidic prelysosomal vacuoles","volume":"32","author":"Marsh","year":"1983","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.virol.2005.11.051","article-title":"Venezuelan equine encephalitis virus entry mechanism requires late endosome formation and resists cell membrane cholesterol depletion","volume":"347","author":"Kolokoltsov","year":"2006","journal-title":"Virology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0092-8674(02)00660-8","article-title":"Structure of dengue virus: Implications for flavivirus organization, maturation, and fusion","volume":"108","author":"Kuhn","year":"2002","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/375291a0","article-title":"The envelope glycoprotein from tick-borne encephalitis virus at 2 \u00c5 resolution","volume":"375","author":"Rey","year":"1995","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.str.2005.09.014","article-title":"Structure and interactions at the viral surface of the envelope protein E1 of Semliki Forest virus","volume":"14","author":"Roussel","year":"2006","journal-title":"Structure"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1261\/rna.5127104","article-title":"Sindbis virus nucleocapsid assembly: RNA folding promotes capsid protein dimerization","volume":"10","author":"Linger","year":"2004","journal-title":"RNA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0969-2126(96)00059-7","article-title":"Identification of a protein binding site on the surface of the alphavirus nucleocapsid and its implication in virus assembly","volume":"4","author":"Lee","year":"1996","journal-title":"Structure"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1128\/jvi.70.5.2757-2763.1996","article-title":"Identification of a region in the Sindbis virus nucleocapsid protein that is involved in specificity of RNA encapsidation","volume":"70","author":"Owen","year":"1996","journal-title":"J. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1038\/s41467-020-18447-z","article-title":"Multiple capsid protein binding sites mediate selective packaging of the alphavirus genomic RNA","volume":"11","author":"Brown","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/pro.2261","article-title":"A decade and a half of protein intrinsic disorder: Biology still waits for physics","volume":"22","author":"Uversky","year":"2013","journal-title":"Protein. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jmb.2011.09.045","article-title":"Molecular links between the E2 envelope glycoprotein and nucleocapsid core in Sindbis virus","volume":"414","author":"Tang","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.1038\/s41467-018-07704-x","article-title":"Implication for alphavirus host-cell entry and assembly indicated by a 3.5\u00c5 resolution cryo-EM structure","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0092-8674(01)00302-6","article-title":"Locations of carbohydrate sites on alphavirus glycoproteins show that E1 forms an icosahedral scaffold","volume":"105","author":"Pletnev","year":"2001","journal-title":"Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/0042-6822(92)90263-O","article-title":"Identification of a sequence element in the alphavirus core protein which mediates interaction of cores with ribosomes and the disassembly of cores","volume":"191","author":"Wengler","year":"1992","journal-title":"Virology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/viro.1996.0403","article-title":"Analyses of the role of structural changes in the regulation of uncoating and assembly of alphavirus cores","volume":"222","author":"Wengler","year":"1996","journal-title":"Virology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00705-009-0333-9","article-title":"The regulation of disassembly of alphavirus cores","volume":"154","author":"Wengler","year":"2009","journal-title":"Arch. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0042-6822(84)90310-6","article-title":"Identification of a transfer of viral core protein to cellular ribosomes during the early stages of alphavirus infection","volume":"134","author":"Wengler","year":"1984","journal-title":"Virology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5309","DOI":"10.1128\/JVI.73.7.5309-5319.1999","article-title":"In Vitro assembly of alphavirus cores by using nucleocapsid protein expressed in Escherichia coli","volume":"73","author":"Tellinghuisen","year":"1999","journal-title":"J. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8898","DOI":"10.1021\/acsnano.5b02632","article-title":"Self-assembly of an alphavirus core-like particle is distinguished by strong inter-subunit association energy and structural defects","volume":"9","author":"Wang","year":"2015","journal-title":"ACS Nano"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.virol.2010.07.009","article-title":"Structure of a Venezuelan equine encephalitis virus assembly intermediate isolated from infected cells","volume":"406","author":"Lamb","year":"2010","journal-title":"Virology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1128\/JVI.77.1.659-664.2003","article-title":"Structure of isolated nucleocapsids from Venezuelan equine encephalitis virus and implications for assembly and disassembly of enveloped virus","volume":"77","author":"Paredes","year":"2003","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"11128","DOI":"10.1128\/JVI.76.21.11128-11132.2002","article-title":"In Vitro-assembled alphavirus core-like particles maintain a structure similar to that of nucleocapsid cores in mature virus","volume":"76","author":"Mukhopadhyay","year":"2002","journal-title":"J. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1515\/znc-1980-1-227","article-title":"Separation of alphavirus nucleocapsids from envelope fragments","volume":"35","author":"Enzmann","year":"1980","journal-title":"Z. Naturforsch C Biosci."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Button, J.M., and Mukhopadhyay, S. (2020). Removing the polyanionic cargo requirement for assembly of alphavirus core-like particles to make an empty alphavirus core. Viruses, 12.","DOI":"10.3390\/v12080846"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"484003","DOI":"10.1088\/1361-648X\/aa90d0","article-title":"Length of encapsidated cargo impacts stability and structure of in vitro assembled alphavirus core-like particles","volume":"29","author":"Rayaprolu","year":"2017","journal-title":"J. Phys. Condens. Matter."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7049","DOI":"10.1128\/jvi.66.12.7049-7058.1992","article-title":"Role of ribosomes in Semliki Forest virus nucleocapsid uncoating","volume":"66","author":"Singh","year":"1992","journal-title":"J. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1172\/JCI200113530","article-title":"Molecular diversity of heparan sulfate","volume":"108","author":"Esko","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1152\/physrev.1991.71.2.481","article-title":"Glycosaminoglycans: Molecular properties, protein interactions, and role in physiological processes","volume":"71","author":"Jackson","year":"1991","journal-title":"Physiol. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1128\/JVI.02494-06","article-title":"Heparan sulfate binding can contribute to the neurovirulence of neuroadapted and nonneuroadapted Sindbis viruses","volume":"81","author":"Ryman","year":"2007","journal-title":"J. Virol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1006\/viro.2000.0546","article-title":"Mutations in the E2 glycoprotein of Venezuelan equine encephalitis virus confer heparan sulfate interaction, low morbidity, and rapid clearance from blood of mice","volume":"276","author":"Bernard","year":"2000","journal-title":"Virology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6303","DOI":"10.1128\/JVI.75.14.6303-6309.2001","article-title":"An amino acid substitution in the coding region of the E2 glycoprotein adapts Ross River virus to utilize heparan sulfate as an attachment moiety","volume":"75","author":"Heil","year":"2001","journal-title":"J. Virol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"10128","DOI":"10.1128\/JVI.76.20.10128-10137.2002","article-title":"Adaptation of alphaviruses to heparan sulfate: Interaction of Sindbis and Semliki forest viruses with liposomes containing lipid-conjugated heparin","volume":"76","author":"Smit","year":"2002","journal-title":"J. Virol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"16026","DOI":"10.1073\/pnas.1110617108","article-title":"Heparan sulfate binding by natural Eastern equine encephalitis viruses promotes neurovirulence","volume":"108","author":"Gardner","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"8582","DOI":"10.1128\/JVI.00937-13","article-title":"Natural variation in the heparan sulfate binding domain of the Eastern equine encephalitis virus E2 glycoprotein alters interactions with cell surfaces and virulence in mice","volume":"87","author":"Gardner","year":"2013","journal-title":"J. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"8890","DOI":"10.1073\/pnas.1910670117","article-title":"Cryo-EM structure of Eastern equine encephalitis virus in complex with heparan sulfate analogues","volume":"117","author":"Chen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1055\/s-0037-1614170","article-title":"Characterization of unfractionated heparin: Comparison of materials from the last 50 years","volume":"84","author":"Mulloy","year":"2000","journal-title":"Thromb. Haemost"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Aksnes, I., Markussen, T., Braaen, S., and Rimstad, E. (2020). Mutation of N-glycosylation sites in salmonid alphavirus (SAV) envelope proteins attenuate the virus in cell culture. Viruses, 12.","DOI":"10.3390\/v12101071"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6206","DOI":"10.1016\/j.vaccine.2014.09.026","article-title":"Salmonid alphavirus glycoprotein E2 requires low temperature and E1 for virion formation and induction of protective immunity","volume":"32","author":"Hikke","year":"2014","journal-title":"Vaccine"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1099\/jgv.0.000412","article-title":"Role of envelope N-linked glycosylation in Ross River virus virulence and transmission","volume":"97","author":"Nelson","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5640","DOI":"10.1128\/JVI.02427-08","article-title":"Role of N-linked glycosylation for sindbis virus infection and replication in vertebrate and invertebrate systems","volume":"83","author":"Knight","year":"2009","journal-title":"J. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BF01315564","article-title":"Investigation of the role of glycans for the biological activity of Semliki Forest virus grown in Aedes albopictus cells using inhibitors of asparagine-linked oligosaccharides trimming","volume":"102","author":"Naim","year":"1988","journal-title":"Arch. Virol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"12022","DOI":"10.1128\/JVI.77.22.12022-12032.2003","article-title":"DC-SIGN and L-SIGN can act as attachment receptors for alphaviruses and distinguish between mosquito cell- and mammalian cell-derived viruses","volume":"77","author":"Klimstra","year":"2003","journal-title":"J. Virol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.4049\/jimmunol.168.5.2118","article-title":"The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells","volume":"168","author":"Engering","year":"2002","journal-title":"J. Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1084\/jem.193.6.671","article-title":"A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection","volume":"193","author":"Bashirova","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/path.1026","article-title":"Placental expression of DC-SIGN may mediate intrauterine vertical transmission of HIV","volume":"195","author":"Soilleux","year":"2001","journal-title":"J. Pathol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nri723","article-title":"C-type lectin receptors on dendritic cells and Langerhans cells","volume":"2","author":"Figdor","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"8356","DOI":"10.1073\/pnas.89.17.8356","article-title":"Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120","volume":"89","author":"Curtis","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1126\/science.1066371","article-title":"Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR","volume":"294","author":"Feinberg","year":"2001","journal-title":"Science"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"28939","DOI":"10.1074\/jbc.M104565200","article-title":"A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands","volume":"276","author":"Mitchell","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1073\/pnas.78.4.2062","article-title":"Nucleotide sequence of the 26S mRNA of Sindbis virus and deduced sequence of the encoded virus structural proteins","volume":"78","author":"Rice","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/BF01321117","article-title":"Asparagine-linked oligosaccharides of Semliki Forest virus grown in mosquito cells","volume":"122","author":"Naim","year":"1992","journal-title":"Arch. Virol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"10634","DOI":"10.1128\/JVI.01323-08","article-title":"Eastern and Venezuelan equine encephalitis viruses differ in their ability to infect dendritic cells and macrophages: Impact of altered cell tropism on pathogenesis","volume":"82","author":"Gardner","year":"2008","journal-title":"J. Virol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1021\/pr401162k","article-title":"Structural plasticity of the Semliki Forest virus glycome upon interspecies transmission","volume":"13","author":"Crispin","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Powell, L.A., Fox, J.M., Kose, N., Kim, A.S., Majedi, M., Bombardi, R., Carnahan, R.H., Slaughter, J.C., Morrison, T.E., and Diamond, M.S. (2020). Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008517"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1084\/jem.20190736","article-title":"Neutralizing antibodies against Mayaro virus require Fc effector functions for protective activity","volume":"216","author":"Earnest","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Burke, C.W., Froude, J.W., Miethe, S., Hulseweh, B., Hust, M., and Glass, P.J. (2018). Human-like neutralizing antibodies protect mice from aerosol exposure with Western equine encephalitis virus. Viruses, 10.","DOI":"10.3390\/v10040147"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"718","DOI":"10.4161\/mabs.28170","article-title":"Human-like antibodies neutralizing Western equine encephalitis virus","volume":"6","author":"Hulseweh","year":"2014","journal-title":"MAbs"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/0042-6822(85)90342-3","article-title":"Biochemical and biological characteristics of epitopes on the E1 glycoprotein of Western equine encephalitis virus","volume":"142","author":"Hunt","year":"1985","journal-title":"Virology"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Broeckel, R., Fox, J.M., Haese, N., Kreklywich, C.N., Sukulpovi-Petty, S., Legasse, A., Smith, P.P., Denton, M., Corvey, C., and Krishnan, S. (2017). Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of Chikungunya virus disease in rhesus macaques. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005637"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"14364","DOI":"10.1128\/JVI.01943-14","article-title":"Exposure of epitope residues on the outer face of the Chikungunya virus envelope trimer determines antibody neutralizing efficacy","volume":"88","author":"Fong","year":"2014","journal-title":"J. Virol."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Fox, J.M., Roy, V., Gunn, B.M., Huang, L., Edeling, M.A., Mack, M., Fremont, D.H., Doranz, B.J., Johnson, S., and Alter, G. (2019). Optimal therapeutic activity of monoclonal antibodies against Chikungunya virus requires Fc-Fc\u03b3R interaction on monocytes. Sci. Immunol., 4.","DOI":"10.1126\/sciimmunol.aav5062"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1016\/j.celrep.2015.11.043","article-title":"Neutralizing monoclonal antibodies block Chikungunya virus entry and release by targeting an epitope critical to viral pathogenesis","volume":"13","author":"Jin","year":"2015","journal-title":"Cell Rep."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Kose, N., Fox, J.M., Sapparapu, G., Bombardi, R., Tennekoon, R.N., de Silva, A.D., Elbashir, S.M., Theisen, M.A., Humphris-Narayanan, E., and Ciaramella, G. (2019). A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against Chikungunya infection. Sci. Immunol., 4.","DOI":"10.1126\/sciimmunol.aaw6647"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"13898","DOI":"10.1073\/pnas.1515558112","article-title":"Cryo-EM structures elucidate neutralizing mechanisms of anti-chikungunya human monoclonal antibodies with therapeutic activity","volume":"112","author":"Long","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Pal, P., Dowd, K.A., Brien, J.D., Edeling, M.A., Gorlatov, S., Johnson, S., Lee, I., Akahata, W., Nabel, G.J., and Richter, M.K. (2013). Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003312"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Quiroz, J.A., Malonis, R.J., Thackray, L.B., Cohen, C.A., Pallesen, J., Jangra, R.K., Brown, R.S., Hofmann, D., Holtsberg, F.W., and Shulenin, S. (2019). Human monoclonal antibodies against Chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1008061"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Selvarajah, S., Sexton, N.R., Kahle, K.M., Fong, R.H., Mattia, K.A., Gardner, J., Lu, K., Liss, N.M., Salvador, B., and Tucker, D.F. (2013). A neutralizing monoclonal antibody targeting the acid-sensitive region in Chikungunya virus E2 protects from disease. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002423"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.chom.2015.06.009","article-title":"Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against Chikungunya virus","volume":"18","author":"Smith","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/BF01309462","article-title":"Localization of four antigenic sites involved in Venezuelan equine encephalomyelitis virus protection","volume":"139","author":"Agapov","year":"1994","journal-title":"Arch. Virol."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Burke, C.W., Froude, J.W., Rossi, F., White, C.E., Moyer, C.L., Ennis, J., Pitt, M.L., Streatfield, S., Jones, R.M., and Musiychuk, K. (2019). Therapeutic monoclonal antibody treatment protects nonhuman primates from severe Venezuelan equine encephalitis virus disease after aerosol exposure. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1008157"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0042-6822(91)90775-7","article-title":"Synthetic peptides of the E2 glycoprotein of Venezuelan equine encephalomyelitis virus. II. Antibody to the amino terminus protects animals by limiting viral replication","volume":"185","author":"Hunt","year":"1991","journal-title":"Virology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"9616","DOI":"10.1128\/JVI.01286-14","article-title":"Locking and blocking the viral landscape of an alphavirus with neutralizing antibodies","volume":"88","author":"Porta","year":"2014","journal-title":"J. Virol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"6359","DOI":"10.1007\/s00253-013-4819-8","article-title":"Analysis of murine B-cell epitopes on Eastern equine encephalitis virus glycoprotein E2","volume":"97","author":"EnCheng","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1007\/BF01718225","article-title":"Glycoproteins E2 of the Venezuelan and Eastern equine encephalomyelitis viruses contain multiple cross-reactive epitopes","volume":"141","author":"Pereboev","year":"1996","journal-title":"Arch. Virol."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Sun, E., Zhao, J., Sun, L., Xu, Q., Yang, T., Qin, Y., Wang, W., Wei, P., Sun, J., and Wu, D. (2013). Comprehensive mapping of common immunodominant epitopes in the Eastern equine encephalitis virus E2 protein recognized by avian antibody responses. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069349"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.vetimm.2012.06.021","article-title":"Phage display identifies an Eastern equine encephalitis virus glycoprotein E2-specific B cell epitope","volume":"148","author":"Zhao","year":"2012","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"27637","DOI":"10.1073\/pnas.2008051117","article-title":"Structural basis of Chikungunya virus inhibition by monoclonal antibodies","volume":"117","author":"Zhou","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrmicro1067","article-title":"A structural perspective of the flavivirus life cycle","volume":"3","author":"Mukhopadhyay","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nature17994","article-title":"Structure of the thermally stable Zika virus","volume":"533","author":"Kostyuchenko","year":"2016","journal-title":"Nature"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1126\/science.1089316","article-title":"Structure of West Nile virus","volume":"302","author":"Mukhopadhyay","year":"2003","journal-title":"Science"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1126\/science.aaf5316","article-title":"The 3.8 \u00c5 resolution cryo-EM structure of Zika virus","volume":"352","author":"Sirohi","year":"2016","journal-title":"Science"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41467-017-00024-6","article-title":"Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/s41467-018-02882-0","article-title":"Structure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody","volume":"9","author":"Fuzik","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/iub.1556","article-title":"Molecular basis of antibody-mediated neutralization and protection against flavivirus","volume":"68","author":"Dai","year":"2016","journal-title":"IUBMB Life"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.cell.2018.02.054","article-title":"Common features of enveloped viruses and implications for immunogen design for next-generation vaccines","volume":"172","author":"Rey","year":"2018","journal-title":"Cell"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/8\/973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:38:28Z","timestamp":1760164708000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/8\/973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,31]]},"references-count":163,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["pathogens10080973"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10080973","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,31]]}}}