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Adenovirus interactions with CD46 on transgenic mouse erythrocytes
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
2010 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 402, no 1, 20-25 p.Article in journal (Refereed) Published
Abstract [en]

Hemagglutination is an established method but has not been used previously to determine the efficacy of virus binding to a specific cellular receptor. Here we have utilized CD46-expressing erythrocytes from a transgenic mouse to establish whether and to what extent the species B adenoviruses (Ads) as well as Ad37 and Ad49 of species D can interact with CD46. A number of different agglutination patterns, and hence CD46 interactions, could be observed for the different adenovirus types. In this system Ad7p, Ad11a, and Ad14 did not agglutinate mouse erythrocytes at all. Hemagglutination of CD46 expressing erythrocytes with high efficiency was observed for the previously established CD46 users Ad11p and Ad35 as well as for the less investigated Ad34. Ad50 agglutinated with moderate efficiency. Ad16, Ad21 and Ad49 gave incomplete agglutination. Ad16 was the only adenovirus that could be eluted. No specific CD46 interaction could be observed for Ad3p or for Ad37.

Place, publisher, year, edition, pages
2010. Vol. 402, no 1, 20-25 p.
Keyword [en]
Adenovirus, CD46, Hemagglutination
National Category
Microbiology in the medical area
URN: urn:nbn:se:umu:diva-33397DOI: 10.1016/j.virol.2010.03.004ISI: 000277967500003PubMedID: 20347110OAI: diva2:311733
Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2010-09-03Bibliographically approved
In thesis
1. Human adenoviruses: new bioassays for antiviral screening and CD46 interaction
Open this publication in new window or tab >>Human adenoviruses: new bioassays for antiviral screening and CD46 interaction
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Adenoviruses are common pathogens all over the world. The majority of the population has at some point been infected with an adenovirus. Although severe disease can occur in otherwise healthy individuals an adenovirus infection is most commonly self limited in these cases. For immunocompromised individuals however, adenoviruses can be life-threatening pathogens capable of causing disseminated disease and multiple organ failure. Still there is no approved drug specific for treatment of adenovirus infections. We have addressed this using a unique whole cell viral replication reporter gene assay to screen small organic molecules for anti-adenoviral effect. This RCAd11pGFP-vector based assay allowed screening without any preconceived idea of the mechanism for adenovirus inhibition. As a result of the screening campaign 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid turned out to be a potent inhibitor of adenoviral replication. To establish a structure-activity relationship a number of analogs were synthesized and evaluated for their anti-adenoviral effect. The carboxylic acid moiety of the molecule was important for efficient inhibition of adenovirus replication.

There are 54 adenovirus types characterized today and these are divided into seven species, A-G. The receptors used by species B and other adenoviruses are not fully characterized. CD46 is a complement regulatory molecule suggested to be used by all species B types and some species D types but this is not established. We have designed a new bioassay for assessment of the interaction between adenoviruses and CD46 and investigated the CD46-binding capacity of adenovirus types indicated to interact with CD46. We concluded that Ad11p, Ad34, Ad35, and Ad50 clearly bind CD46 specifically, whereas Ad3p, Ad7p, Ad14, and Ad37 do not.

CD46 is expressed on all human nucleated cells and serves as a receptor for a number of different bacteria and viruses. Downregulation of CD46 on the cell surface occurs upon binding by some of these pathogens. We show that early in infection Ad11p virions downregulate CD46 upon binding to a much higher extent than the complement regulatory molecules CD55 and CD59.

These findings may lead to a better understanding of the pathogenesis of adenoviruses in general and species B adenoviruses in particular and hopefully we have discovered a molecule that can be the basis for development of new anti-adenoviral drugs.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2010. 81 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1366
Adenovirus, CD46, hemagglutination, antiviral, small molecule, screening
National Category
Microbiology in the medical area
urn:nbn:se:umu:diva-35733 (URN)978-91-7459-056-2 (ISBN)
Public defence
2010-09-24, Sal 914, 9tr NUS, Umeå, 09:00 (English)
Available from: 2010-09-03 Created: 2010-09-01 Last updated: 2014-04-25Bibliographically approved

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Andersson, Emma KMei, Ya-FangWadell, Göran
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