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dc.date.accessioned2020-06-09T18:13:23Z
dc.date.available2020-06-09T18:13:23Z
dc.date.created2019-09-02T10:35:42Z
dc.date.issued2019
dc.identifier.citationBottermann, Maria Foss, Stian Caddy, Sarah L. Clift, Dean van Tienen, Laurens M. Vaysburd, Marina Cruickshank, James Kennedy O'Connell, Kevin Clark, Jessica Mayes, Keith Higginson, Katie Lode, Heidrun Elisabeth McAdam, Martin Berner Sandlie, Inger Andersen, Jan Terje James, Leo C. . Complement C4 prevents viral infection through capsid inactivation. Cell Host and Microbe. 2019, 25(4), 617-629
dc.identifier.urihttp://hdl.handle.net/10852/76826
dc.description.abstractThe complement system is vital for anti-microbial defense. In the classical pathway, pathogen-bound antibody recruits the C1 complex (C1qC1r2C1s2) that initiates a cleavage cascade involving C2, C3, C4, and C5 and triggering microbial clearance. We demonstrate a C4-dependent antiviral mechanism that is independent of downstream complement components. C4 inhibits human adenovirus infection by directly inactivating the virus capsid. Rapid C4 activation and capsid deposition of cleaved C4b are catalyzed by antibodies via the classical pathway. Capsid-deposited C4b neutralizes infection independent of C2 and C3 but requires C1q antibody engagement. C4b inhibits capsid disassembly, preventing endosomal escape and cytosolic access. C4-deficient mice exhibit heightened viral burdens. Additionally, complement synergizes with the Fc receptor TRIM21 to block transduction by an adenovirus gene therapy vector but is partially restored by Fab virus shielding. These results suggest that the complement system could be altered to prevent virus infection and enhance virus gene therapy efficacy.
dc.languageEN
dc.publisherCell Press
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleComplement C4 prevents viral infection through capsid inactivation
dc.typeJournal article
dc.creator.authorBottermann, Maria
dc.creator.authorFoss, Stian
dc.creator.authorCaddy, Sarah L.
dc.creator.authorClift, Dean
dc.creator.authorvan Tienen, Laurens M.
dc.creator.authorVaysburd, Marina
dc.creator.authorCruickshank, James Kennedy
dc.creator.authorO'Connell, Kevin
dc.creator.authorClark, Jessica
dc.creator.authorMayes, Keith
dc.creator.authorHigginson, Katie
dc.creator.authorLode, Heidrun Elisabeth
dc.creator.authorMcAdam, Martin Berner
dc.creator.authorSandlie, Inger
dc.creator.authorAndersen, Jan Terje
dc.creator.authorJames, Leo C.
cristin.unitcode185,15,29,0
cristin.unitnameInstitutt for biovitenskap
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.cristin1720481
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Cell Host and Microbe&rft.volume=25&rft.spage=617&rft.date=2019
dc.identifier.jtitleCell Host and Microbe
dc.identifier.volume25
dc.identifier.issue4
dc.identifier.startpage617
dc.identifier.endpage629.e7
dc.identifier.doihttps://doi.org/10.1016/j.chom.2019.02.016
dc.identifier.urnURN:NBN:no-79955
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn1931-3128
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/76826/2/Bottermann_Sandlie_Andersen%2BFAR_Cristin-post%2B1720481.pdf
dc.type.versionPublishedVersion
dc.relation.projectNFR/179573
dc.relation.projectNFR/230526
dc.relation.projectNFR/251037


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Attribution 4.0 International
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