Enteric Species F Human Adenoviruses use Laminin-Binding Integrins as Co-Receptors for Infection of Ht-29 Cells

Anandi Rajan, B. David Persson, Lars Frängsmyr, Annelie Olofsson, Linda Sandblad, Jyrki Heino, Yoshikazu Takada, A. Paul Mould, Lynn M. Schnapp, Jason Gall, Niklas Arnberg

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4 Scopus citations

Abstract

The enteric species F human adenovirus types 40 and 41 (HAdV-40 and -41) are the third most common cause of infantile gastroenteritis in the world. Knowledge about HAdV-40 and -41 cellular infection is assumed to be fundamentally different from that of other HAdVs since HAdV-40 and -41 penton bases lack the αV-integrin-interacting RGD motif. This motif is used by other HAdVs mainly for internalization and endosomal escape. We hypothesised that the penton bases of HAdV-40 and -41 interact with integrins independently of the RGD motif. HAdV-41 transduction of a library of rodent cells expressing specific human integrin subunits pointed to the use of laminin-binding α2-, α3- and α6-containing integrins as well as other integrins as candidate co-receptors. Specific laminins prevented internalisation and infection, and recombinant, soluble HAdV-41 penton base proteins prevented infection of human intestinal HT-29 cells. Surface plasmon resonance analysis demonstrated that HAdV-40 and -41 penton base proteins bind to α6-containing integrins with an affinity similar to that of previously characterised penton base:integrin interactions. With these results, we propose that laminin-binding integrins are co-receptors for HAdV-40 and -41.

Original languageEnglish (US)
Article number10019
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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    Rajan, A., Persson, B. D., Frängsmyr, L., Olofsson, A., Sandblad, L., Heino, J., Takada, Y., Mould, A. P., Schnapp, L. M., Gall, J., & Arnberg, N. (2018). Enteric Species F Human Adenoviruses use Laminin-Binding Integrins as Co-Receptors for Infection of Ht-29 Cells. Scientific Reports, 8(1), [10019]. https://doi.org/10.1038/s41598-018-28255-7