Show simple item record

dc.contributor.authorThaa, Bastian
dc.contributor.authorBiasiotto, Roberta
dc.contributor.authorEng, Kai
dc.contributor.authorNeuvonen, Maarit
dc.contributor.authorGotte, Benjamin
dc.contributor.authorRheinemann, Lara
dc.contributor.authorMutso, Margit
dc.contributor.authorUtt, Age
dc.contributor.authorVarghese, Finny
dc.contributor.authorBalistreri, Giuseppe
dc.contributor.authorMerits, Andres
dc.contributor.authorAhola, Tero
dc.contributor.authorMcInerney, Gerald M.
dc.date.accessioned2017-08-14T06:51:23Z
dc.date.available2017-08-14T06:51:23Z
dc.date.issued2015
dc.identifier.issn1098-5514
dc.identifier.doi10.1128/JVI.01579-15
dc.identifier.urihttp://hdl.handle.net/10072/344010
dc.description.abstractMany viruses affect or exploit the phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway, a crucial prosurvival signaling cascade. We report that this pathway was strongly activated in cells upon infection with the Old World alphavirus Semliki Forest virus (SFV), even under conditions of complete nutrient starvation. We mapped this activation to the hyperphosphorylated/acidic domain in the C-terminal tail of SFV nonstructural protein nsP3. Viruses with a deletion of this domain (SFV-Δ50) but not of other regions in nsP3 displayed a clearly delayed and reduced capacity of Akt stimulation. Ectopic expression of the nsP3 of SFV wild type (nsP3-wt), but not nsP3-Δ50, equipped with a membrane anchor was sufficient to activate Akt. We linked PI3K-Akt-mTOR stimulation to the intracellular dynamics of viral replication complexes, which are formed at the plasma membrane and subsequently internalized in a process blocked by the PI3K inhibitor wortmannin. Replication complex internalization was observed upon infection of cells with SFV-wt and SFV mutants with deletions in nsP3 but not with SFV-Δ50, where replication complexes were typically accumulated at the cell periphery. In cells infected with the closely related chikungunya virus (CHIKV), the PI3K-Akt-mTOR pathway was only moderately activated. Replication complexes of CHIKV were predominantly located at the cell periphery. Exchanging the hypervariable C-terminal tail of nsP3 between SFV and CHIKV induced the phenotype of strong PI3K-Akt-mTOR activation and replication complex internalization in CHIKV. In conclusion, infection with SFV but not CHIKV boosts PI3K-Akt-mTOR through the hyperphosphorylated/acidic domain of nsP3 to drive replication complex internalization.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society of Microbiology
dc.relation.ispartofpagefrom11420
dc.relation.ispartofpageto11437
dc.relation.ispartofissue22
dc.relation.ispartofjournalJournal of Virology
dc.relation.ispartofvolume89
dc.subject.fieldofresearchMicrobiology not elsewhere classified
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchAgricultural and Veterinary Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode060599
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode07
dc.subject.fieldofresearchcode11
dc.titleDifferential phosphatidylinositol-3-kinase-Akt-mTOR activation by Semliki Forest and Chikungunya viruses is dependent on nsP3 and connected to replication complex internalization
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2015 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorMutso, Margit


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record