{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T01:23:53Z","timestamp":1789867433402,"version":"4.0.1"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI051967"],"award-info":[{"award-number":["T32AI051967"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"DOD | Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-13-1-0005"],"award-info":[{"award-number":["HDTRA1-13-1-0005"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The alphaviruses Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV) are arthropod-borne positive-strand RNA viruses that are capable of causing acute and fatal encephalitis in many mammals, including humans. VEEV was weaponized during the Cold War and is recognized as a select agent. Currently, there are no FDA-approved vaccines or therapeutics for these viruses. The spread of VEEV and other members of this family due to climate change-mediated vector range expansion underscores the need for research aimed at developing medical countermeasures. These viruses utilize programmed \u22121 ribosomal frameshifting (\u22121 PRF) to synthesize the viral\n                    <jats:italic>trans<\/jats:italic>\n                    -frame (TF) protein, which has previously been shown to be important for neuropathogenesis in the related Sindbis virus. Here, the alphavirus \u22121 PRF signals were characterized, revealing novel \u22121 PRF stimulatory structures. \u22121 PRF attenuation mildly affected the kinetics of VEEV accumulation in cultured cells but strongly inhibited its pathogenesis in an aerosol infection mouse model. Importantly, the decreased viral titers in the brains of mice infected with the mutant virus suggest that the alphavirus TF protein is important for passage through the blood-brain barrier and\/or for neuroinvasiveness. These findings suggest a novel approach to the development of safe and effective live attenuated vaccines directed against VEEV and perhaps other closely related \u22121 PRF-utilizing viruses.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Venezuelan equine encephalitis virus (VEEV) is a select agent that has been weaponized. This arthropod-borne positive-strand RNA virus causes acute and fatal encephalitis in many mammals, including humans. There is no vaccine or other approved therapeutic. VEEV and related alphaviruses utilize programmed \u22121 ribosomal frameshifting (\u22121 PRF) to synthesize the viral\n                    <jats:italic>trans<\/jats:italic>\n                    -frame (TF) protein, which is important for neuropathogenesis. \u22121 PRF attenuation strongly inhibited VEEV pathogenesis in mice, and viral replication analyses suggest that the TF protein is critical for neurological disease. These findings suggest a new approach to the development of safe and effective live attenuated vaccines directed against VEEV and other related viruses.\n                  <\/jats:p>","DOI":"10.1128\/jvi.01766-16","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T23:00:46Z","timestamp":1479337246000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Ablation of Programmed \u22121 Ribosomal Frameshifting in Venezuelan Equine Encephalitis Virus Results in Attenuated Neuropathogenicity"],"prefix":"10.1128","volume":"91","author":[{"given":"Joseph A.","family":"Kendra","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwini","family":"Brahms","sequence":"additional","affiliation":[{"name":"National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Woodson","sequence":"additional","affiliation":[{"name":"National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Bell","sequence":"additional","affiliation":[{"name":"National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousuf A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"MRIGlobal, Global Health Security, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylene","family":"Kehn-Hall","sequence":"additional","affiliation":[{"name":"National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2402-9698","authenticated-orcid":false,"given":"Jonathan D.","family":"Dinman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2009.08.023"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1179"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.8.3602"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.042499-0"},{"key":"e_1_3_2_6_2","first-page":"521","article-title":"Programmed ribosomal frameshifting goes beyond viruses: organisms from all three kingdoms use frameshifting to regulate gene expression, perhaps signaling a paradigm shift","volume":"1","author":"Dinman JD","year":"2006","unstructured":"Dinman JD . 2006. 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