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

Publisher: NATURE PUBLISHING GROUP

: 2018

: Scientific Reports

: SCIENTIFIC REPORTS

: SCI REP-UK

: ARTN 10019

: 8

: 14

: 2045-2322

DOI: https://doi.org/10.1038/s41598-018-28255-7

: https://research.utu.fi/converis/portal/detail/Publication/32168830

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 aV-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 alpha 2-, alpha 3- and alpha 6- 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 alpha 6-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.

s41598-018-28255-7.pdf