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dc.contributor.authorChiramel, Abhilash I.
dc.contributor.authorMeyerson, Nicholas R.
dc.contributor.authorMcNally, Kristin L.
dc.contributor.authorBroeckel, Rebecca M.
dc.contributor.authorMontoya, Vanessa R.
dc.contributor.authorMendez-Solis, Omayra
dc.contributor.authorRobertson, Shelly J.
dc.contributor.authorSturdevant, Gail L.
dc.contributor.authorLubick, Kirk J.
dc.contributor.authorNair, Vinod
dc.contributor.authorYouseff, Brian H.
dc.contributor.authorIreland, Robin M.
dc.contributor.authorBosio, Catharine M.
dc.contributor.authorKim, Kyusik
dc.contributor.authorLuban, Jeremy
dc.contributor.authorHirsch, Vanessa M.
dc.contributor.authorTaylor, R. Travis
dc.contributor.authorBouamr, Fadila
dc.contributor.authorSawyer, Sara L.
dc.contributor.authorBest, Sonja M.
dc.date2022-08-11T08:10:18.000
dc.date.accessioned2022-08-23T17:03:47Z
dc.date.available2022-08-23T17:03:47Z
dc.date.issued2019-06-11
dc.date.submitted2019-06-27
dc.identifier.citation<p>Cell Rep. 2019 Jun 11;27(11):3269-3283.e6. doi: 10.1016/j.celrep.2019.05.040. <a href="https://doi.org/10.1016/j.celrep.2019.05.040">Link to article on publisher's site</a></p>
dc.identifier.issn2211-1247 (Electronic)
dc.identifier.doi10.1016/j.celrep.2019.05.040
dc.identifier.pmid31189110
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44501
dc.description.abstractTripartite motif-containing protein 5alpha (TRIM5alpha) is a cellular antiviral restriction factor that prevents early events in retrovirus replication. The activity of TRIM5alpha is thought to be limited to retroviruses as a result of highly specific interactions with capsid lattices. In contrast to this current understanding, we show that both human and rhesus macaque TRIM5alpha suppress replication of specific flaviviruses. Multiple viruses in the tick-borne encephalitis complex are sensitive to TRIM5alpha-dependent restriction, but mosquito-borne flaviviruses, including yellow fever, dengue, and Zika viruses, are resistant. TRIM5alpha suppresses replication by binding to the viral protease NS2B/3 to promote its K48-linked ubiquitination and proteasomal degradation. Importantly, TRIM5alpha contributes to the antiviral function of IFN-I against sensitive flaviviruses in human cells. Thus, TRIM5alpha possesses remarkable plasticity in the recognition of diverse virus families, with the potential to influence human susceptibility to emerging flaviviruses of global concern.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31189110&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectTRIM5α
dc.subjectflavivirus
dc.subjectinterferon
dc.subjectinterferon stimulated genes
dc.subjectrestriction factor
dc.subjectretrovirus
dc.subjecttick-borne encephalitis virus
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry
dc.subjectEnzymes and Coenzymes
dc.subjectImmunology and Infectious Disease
dc.subjectMolecular Biology
dc.subjectMolecular Genetics
dc.subjectVirology
dc.titleTRIM5alpha Restricts Flavivirus Replication by Targeting the Viral Protease for Proteasomal Degradation
dc.typeJournal Article
dc.source.journaltitleCell reports
dc.source.volume27
dc.source.issue11
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1096&amp;context=pmm_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pmm_pp/97
dc.identifier.contextkey14823165
refterms.dateFOA2022-08-23T17:03:47Z
html.description.abstract<p>Tripartite motif-containing protein 5alpha (TRIM5alpha) is a cellular antiviral restriction factor that prevents early events in retrovirus replication. The activity of TRIM5alpha is thought to be limited to retroviruses as a result of highly specific interactions with capsid lattices. In contrast to this current understanding, we show that both human and rhesus macaque TRIM5alpha suppress replication of specific flaviviruses. Multiple viruses in the tick-borne encephalitis complex are sensitive to TRIM5alpha-dependent restriction, but mosquito-borne flaviviruses, including yellow fever, dengue, and Zika viruses, are resistant. TRIM5alpha suppresses replication by binding to the viral protease NS2B/3 to promote its K48-linked ubiquitination and proteasomal degradation. Importantly, TRIM5alpha contributes to the antiviral function of IFN-I against sensitive flaviviruses in human cells. Thus, TRIM5alpha possesses remarkable plasticity in the recognition of diverse virus families, with the potential to influence human susceptibility to emerging flaviviruses of global concern.</p>
dc.identifier.submissionpathpmm_pp/97
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages3269-3283.e6


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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).