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Soluble components in body fluids as mediators of adenovirus infections
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
2013 (English)Licentiate thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2013. , 43 p.
National Category
Microbiology in the medical area
Research subject
Medical Virology
Identifiers
URN: urn:nbn:se:umu:diva-70173ISBN: 978-91-7459-661-8 (print)OAI: oai:DiVA.org:umu-70173DiVA: diva2:619805
Presentation
2013-05-17, A103, NUS, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2013-08-05 Created: 2013-05-06 Last updated: 2013-08-05Bibliographically approved
List of papers
1. Coagulation factors IX and X enhance binding and infection of adenovirus types 5 and 31 in human epithelial cells
Open this publication in new window or tab >>Coagulation factors IX and X enhance binding and infection of adenovirus types 5 and 31 in human epithelial cells
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2009 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 83, no 8, 3816-3825 p.Article in journal (Refereed) Published
Abstract [en]

Most adenoviruses bind directly to the coxsackie and adenovirus receptor (CAR) on target cells in vitro, but recent research has shown that adenoviruses can also use soluble components in body fluids for indirect binding to target cells. These mechanisms have been identified upon addressing the questions of how to de- and retarget adenovirus-based vectors for human gene and cancer therapy, but the newly identified mechanisms also suggest that the role of body fluids and their components may also be of importance for natural, primary infections. Here we demonstrate that plasma, saliva, and tear fluid promote binding and infection of adenovirus type 5 (Ad5) in respiratory and ocular epithelial cells, which corresponds to the natural tropism of most adenoviruses, and that plasma promotes infection by Ad31. By using a set of binding and infection experiments, we also found that Ad5 and Ad31 require coagulation factors IX (FIX) or X (FX) or just FIX, respectively, for efficient binding and infection. The concentrations of these factors that were required for maximum binding were 1/100th of the physiological concentrations. Preincubation of virions with heparin or pretreatment of cells with heparinase I indicated that the role of cell surface heparan sulfate during FIX- and FX-mediated adenovirus binding and infection is mechanistically serotype specific. We conclude that the use of coagulation factors by adenoviruses may be of importance not only for the liver tropism seen when administering adenovirus vectors to the circulation but also during primary infections by wild-type viruses of their natural target cell types.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-21099 (URN)10.1128/JVI.02562-08 (DOI)19158249 (PubMedID)
Available from: 2009-04-02 Created: 2009-04-02 Last updated: 2017-12-13Bibliographically approved
2. Coagulation factor IX mediates serotype-specific binding of species A adenoviruses to host cells
Open this publication in new window or tab >>Coagulation factor IX mediates serotype-specific binding of species A adenoviruses to host cells
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2011 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 85, no 24, 13420-13431 p.Article in journal (Refereed) Published
Abstract [en]

Human species A adenoviruses (HAdVs) comprise three serotypes: HAdV-12, -18, and -31. These viruses are common pathogens and cause systemic infections that usually involve the airways and/or intestine. In immunocompromised individuals, species A adenoviruses in general, and HAdV-31 in particular, cause life-threatening infections. By combining binding and infection experiments, we demonstrate that coagulation factor IX (FIX) efficiently enhances binding and infection by HAdV-18 and HAdV-31, but not by HAdV-12, in epithelial cells originating from the airways or intestine. This is markedly different from the mechanism for HAdV-5 and other human adenoviruses, which utilize coagulation factor X (FX) for infection of host cells. Surface plasmon resonance experiments revealed that the affinity of the HAdV-31 hexon-FIX interaction is higher than that of the HAdV-5 hexon-FX interaction and that the half-lives of these interactions are profoundly different. Moreover, both HAdV-31-FIX and HAdV-5-FX complexes bind to heparan sulfate-containing glycosaminoglycans (GAGs) on target cells, but binding studies utilizing cells expressing specific GAGs and GAG-cleaving enzymes revealed differences in GAG dependence and specificity between these two complexes. These findings add to our understanding of the intricate infection pathways used by human adenoviruses, and they may contribute to better design of HAdV-based vectors for gene and cancer therapy. Furthermore, the interaction between the HAdV-31 hexon and FIX may also serve as a target for antiviral treatment.

Place, publisher, year, edition, pages
Washington: The American Society For Microbiology, 2011
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-50925 (URN)10.1128/JVI.06088-11 (DOI)000297642000058 ()
Available from: 2012-01-20 Created: 2012-01-02 Last updated: 2017-12-08Bibliographically approved

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