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dc.contributor.authorCabezas-Falcon, Sheila
dc.contributor.authorNorbury, Aidan J
dc.contributor.authorHulme-Jones, Jarrod
dc.contributor.authorKlebe, Sonja
dc.contributor.authorAdamson, Penelope
dc.contributor.authorRudd, Penny A
dc.contributor.authorMahalingam, Suresh
dc.contributor.authorOng, Li-Ching
dc.contributor.authorAlonso, Sylvie
dc.contributor.authorGordon, David L
dc.contributor.authorCarr, Jillian M
dc.date.accessioned2021-01-13T22:37:57Z
dc.date.available2021-01-13T22:37:57Z
dc.date.issued2021
dc.identifier.issn0022-1317en_US
dc.identifier.doi10.1099/jgv.0.001547en_US
dc.identifier.urihttp://hdl.handle.net/10072/401009
dc.description.abstractThe complement alternative pathway (AP) is tightly regulated and changes in two important AP components, factor B (FB) and factor H (FH) are linked to severe dengue in humans. Here, a mouse model of dengue was investigated to define the changes in FB and FH and assess the utility of this model to study the role of the AP in severe dengue. Throughout the period of viremia in the AG129 IFN signalling-deficient mouse, an increase in FB and a decrease in FH was observed following dengue virus (DENV) infection, with the former only seen in a model of more severe disease associated with antibody-dependent enhancement (ADE). Terminal disease was associated with a decrease in FB and FH, with greater changes during ADE, and accompanied by increased C3 degradation consistent with complement activation. In silico analysis of NFκΒ, signal transducer and activator of transcription (STAT) and IFN-driven FB and FH promoter elements to reflect the likely impact of the lack of IFN-responses in AG129 mice, demonstrated that these elements differed markedly between human and mouse, notably with mouse FH lacking NFκΒ and key IFN-stimulated response elements (ISRE), and FB with many more NFκΒ and STAT-responsive elements than human FB. Thus, the AG129 mouse offers utility in demonstrating changes in FB and FH that, similar to humans, are associated with severe disease, but lack predicted important human-specific and IFN-dependent responses of FB and FH to DENV-infection that are likely to regulate the subtleties of the overall AP response during dengue disease in humans.en_US
dc.description.peerreviewedYesen_US
dc.languageenen_US
dc.publisherMicrobiology Societyen_US
dc.relation.ispartofjournalJournal of General Virologyen_US
dc.subject.fieldofresearchBiological Sciencesen_US
dc.subject.fieldofresearchAgricultural and Veterinary Sciencesen_US
dc.subject.fieldofresearchMedical and Health Sciencesen_US
dc.subject.fieldofresearchcode06en_US
dc.subject.fieldofresearchcode07en_US
dc.subject.fieldofresearchcode11en_US
dc.titleChanges in complement alternative pathway components, factor B and factor H during dengue virus infection in the AG129 mouseen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
dcterms.bibliographicCitationCabezas-Falcon, S; Norbury, AJ; Hulme-Jones, J; Klebe, S; Adamson, P; Rudd, PA; Mahalingam, S; Ong, L-C; Alonso, S; Gordon, DL; Carr, JM, Changes in complement alternative pathway components, factor B and factor H during dengue virus infection in the AG129 mouse, Journal of General Virology, 2021en_US
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/en_US
dc.date.updated2021-01-13T04:47:08Z
dc.description.versionPublisheden_US
gro.description.notepublicThis publication has been entered as an advanced online version in Griffith Research Online.en_US
gro.rights.copyright© 2021 The Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.en_US
gro.hasfulltextFull Text
gro.griffith.authorMahalingam, Suresh
gro.griffith.authorRudd, Penny A.


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