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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-48705

Lütschg, V; Boucke, K; Hemmi, S; Greber, U F (2011). Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells. Nature Communications, 2:391.

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Mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the luminal space. Here we show that human adenovirus type 5 engages an antiviral immune response to enter polarized epithelial cells. Blood-derived macrophages co-cultured apically on polarized epithelial cells facilitate epithelial infection. Infection also occurs in the absence of macrophages, if virus-conditioned macrophage-medium containing the chemotactic cytokine CXCL8 (interleukin-8), or recombinant CXCL8 are present. In polarized cells, CXCL8 activates a Src-family tyrosine kinase via the apical CXCR1 and CXCR2 receptors. This activation process relocates the viral co-receptor ανβ3 integrin to the apical surface, and enables apical binding and infection with adenovirus depending on the primary adenovirus receptor CAR. This paradigm may explain how other mucosal pathogens enter epithelial cells.


34 citations in Web of Science®
38 citations in Scopus®
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210 downloads since deposited on 19 Jul 2011
37 downloads since 12 months

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Deposited On:19 Jul 2011 07:17
Last Modified:05 Apr 2016 14:57
Publisher:Nature Publishing Group
Publisher DOI:10.1038/ncomms1391
PubMed ID:21750545

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