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The Arg279Gln [corrected] substitution in the adenovirus type 11p (Ad11p) fiber knob abolishes EDTA-resistant binding to A549 and CHO-CD46 cells, converting the phenotype to that of Ad7p.
Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
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2006 (English)In: Journal of Virology, ISSN 0022-538X, Vol. 80, no 4, 1897-905 p.Article in journal (Refereed) Published
Abstract [en]

The major determinant of adenovirus (Ad) attachment to host cells is the C-terminal knob domain of the trimeric fiber protein. Ad type 11p (Ad11p; species B2) in contrast to Ad7p (species B1) utilizes at least two different cellular attachment receptors, designated sBAR (species B adenovirus receptor) and sB2AR (species B2 adenovirus receptor). CD46 has recently been identified as one of the Ad11p attachment receptors. However, CD46 did not seem to constitute a functional receptor for Ad7p. Although Ad7p shares high knob amino acid identity with Ad11p, Ad7p is deficient in binding to both sB2AR and CD46. To determine what regions of the Ad11p fiber knob are necessary for sB2AR-CD46 interaction, we constructed recombinant fiber knobs (rFK) with Ad11p/Ad7p chimeras and Ad11p sequences having a single amino acid substitution from Ad7p. Binding of the constructs to A549 and CHO-CD46 BC1 isoform-expressing cells was analyzed by flow cytometry. Our results indicate that an Arg279Gln [corrected] substitution is sufficient to convert the Ad11p receptor-interaction phenotype to that of Ad7p and abolish sB2AR and CD46 interaction. Also a Glu279Arg substitution in Ad7p rFKs increases CD46 binding. Thus, the lateral HI loop of the Ad11p fiber knob seems to be the key determinant for Ad11p sB2AR-CD46 interaction. This result is comparable to another non-coxsackie-adenovirus receptor binding Ad (Ad37p), where substitution of one amino acid abolishes virus-cell interaction. In conjunction with previous results, our findings also strongly suggest that sB2AR is equivalent to CD46.

Place, publisher, year, edition, pages
2006. Vol. 80, no 4, 1897-905 p.
URN: urn:nbn:se:umu:diva-20670DOI: 10.1128/JVI.80.4.1897-1905.2006PubMedID: 16439545OAI: diva2:209278
Available from: 2009-03-24 Created: 2009-03-24 Last updated: 2012-02-10
In thesis
1. Adenovirus species B interactions with CD46
Open this publication in new window or tab >>Adenovirus species B interactions with CD46
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Adenoviruses (Ad) are double-stranded (ds) DNA, non-enveloped viruses. There are seven species (A-G) of human Ads with 52 knownserotypes to date. Human Ads cause a broad range of pathologies, ranging from upper respiratory tract infections to persistent urinary tract infections. The main determinant for Ads tropism in vitro is the protruding, antenna-like, fiber protein. The fiberknob is responsible for the main interaction with the attachment receptor of the host cell. Most Ad species use the coxsackie- adenovirus receptor (CAR) as their main attachment receptor. Most species B Ads, however use CD46. CD46 is a cell surface complement regulatory protein, which is expressed on all nucleated cells in humans. Species B Ads exhibit a low seroprevalenc in the human population, making these Ads promising vector candidates for gene therapy. We have studied human Ad species B members, serotypes 7 and 11 (Ad7 and Ad11), as well as their interaction with CD46. Our first experiments showed that all species B Ads use CD46 as their main attachment receptor, with the exception of Ad3 and Ad7. Second, we performed mutational studies of recombinant Ad11p fiberknobs. These studies showed that arginine 279 in the Ad 11 fiberknob is necessary for CD46 binding. Finally we studied the effect of Ad11 binding to CD46. The results indicate that CD46 is rapidly downregulated on the cell surface after Ad11 binding. These results may provide a further understanding of the basic biology and pathology of species B Ads and may also be useful in construction of gene therapy vectors based on species B Ads.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2012. 84 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1480
Adenovirus 11, CD46
National Category
Research subject
urn:nbn:se:umu:diva-52075 (URN)978-91-7459-368-6 (ISBN)
Public defence
2012-03-02, Sal E04, Biomedicinhuset, Byggnad 6E, Norrlands universitetssjukhus, Umeå, 20:42 (English)
Available from: 2012-02-10 Created: 2012-02-08 Last updated: 2012-02-10Bibliographically approved

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