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dc.contributor.authorMazzon, Michela
dc.contributor.authorCastro, Cecilia
dc.contributor.authorThaa, Bastian
dc.contributor.authorLiu, Lifeng
dc.contributor.authorMutso, Margit
dc.contributor.authorLiu, Xiang
dc.contributor.authorMahalingam, Suresh
dc.contributor.authorGriffin, Julian L
dc.contributor.authorMarsh, Mark
dc.contributor.authorMcInerney, Gerald M
dc.date.accessioned2019-07-05T12:30:52Z
dc.date.available2019-07-05T12:30:52Z
dc.date.issued2018
dc.identifier.issn1553-7366
dc.identifier.doi10.1371/journal.ppat.1006835
dc.identifier.urihttp://hdl.handle.net/10072/381320
dc.description.abstractVirus reprogramming of cellular metabolism is recognised as a critical determinant for viral growth. While most viruses appear to activate central energy metabolism, different viruses have been shown to rely on alternative mechanisms of metabolic activation. Whether related viruses exploit conserved mechanisms and induce similar metabolic changes is currently unclear. In this work we investigate how two alphaviruses, Semliki Forest virus and Ross River virus, reprogram host metabolism and define the molecular mechanisms responsible. We demonstrate that in both cases the presence of a YXXM motif in the viral protein nsP3 is necessary for binding to the PI3K regulatory subunit p85 and for activating AKT. This leads to an increase in glucose metabolism towards the synthesis of fatty acids, although additional mechanisms of metabolic activation appear to be involved in Ross River virus infection. Importantly, a Ross River virus mutant that fails to activate AKT has an attenuated phenotype in vivo, suggesting that viral activation of PI3K/AKT contributes to virulence and disease.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto22
dc.relation.ispartofissue1
dc.relation.ispartofjournalPLoS Pathogens
dc.relation.ispartofvolume14
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchMicrobiology not elsewhere classified
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchcode3107
dc.subject.fieldofresearchcode310799
dc.subject.fieldofresearchcode3204
dc.subject.fieldofresearchcode3207
dc.titleAlphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2018 Mazzon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorMahalingam, Suresh
gro.griffith.authorLiu, Xiang
gro.griffith.authorMutso, Margit


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