Show simple item record

dc.contributor.authorTan, MJA
dc.contributor.authorBrown, NG
dc.contributor.authorChan, KWK
dc.contributor.authorJin, JY
dc.contributor.authorKong, SYZ
dc.contributor.authorVasudevan, SG
dc.date.accessioned2021-06-04T01:51:54Z
dc.date.available2021-06-04T01:51:54Z
dc.date.issued2020
dc.identifier.issn0022-1317
dc.identifier.doi10.1099/jgv.0.001462
dc.identifier.urihttp://hdl.handle.net/10072/404927
dc.description.abstractThe dengue virus (DENV) replication complex is made up of its non-structural (NS) proteins and yet-to- be identified host proteins, but the molecular interactions between these proteins are not fully elucidated. In this work, we sought to uncover the interactions between DENV NS1 and its fellow NS proteins using a yeast two-hybrid (Y2H) approach, and found that domain II of NS1 binds to an N-terminal cytoplasmic fragment of NS4A. Mutations in amino acid residues 41 and 43 in this cytoplasmic region of NS4A disrupted the interaction between NS1 and the NS4A-2K- 4B precursor protein. When the NS4A Y41F mutation was introduced into the context of the virus via a DENV2 infectious clone, this mutant virus exhibited impaired viral fitness and decreased infectious virus production. The NS4A Y41F mutant virus triggered a significantly muted transcriptional activation of interferon-stimulated genes compared to wild-type virus that is independent of NS4A's ability to antagonize type I interferon signalling. Taken together, we have identified a link between DENV NS1 and the cytoplasmic domain in NS4A that is important for its cellular and viral functions.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherMicrobiology Society
dc.relation.ispartofpagefrom941
dc.relation.ispartofpageto953
dc.relation.ispartofissue9
dc.relation.ispartofjournalJournal of General Virology
dc.relation.ispartofvolume101
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchAgricultural, veterinary and food sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode30
dc.subject.fieldofresearchcode32
dc.subject.keywordsNS1
dc.subject.keywordsNS4A
dc.subject.keywordsdengue virus (DENV)
dc.subject.keywordsflavivirus
dc.titleMutations in the cytoplasmic domain of dengue virus NS4A affect virus fitness and interactions with other non-structural proteins
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationTan, MJA; Brown, NG; Chan, KWK; Jin, JY; Kong, SYZ; Vasudevan, SG, Mutations in the cytoplasmic domain of dengue virus NS4A affect virus fitness and interactions with other non-structural proteins, Journal of General Virology, 2020, 101 (9), pp. 941-953
dc.date.updated2021-06-03T23:47:35Z
gro.hasfulltextNo Full Text
gro.griffith.authorVasudevan, Subhash


Files in this item

FilesSizeFormatView

There are no files associated with 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