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Integrin alpha5beta1-mediated adenovirus infection is enhanced by the integrin-activating antibody TS2/16
E Davison1, R M Diaz, I R Hart
1Department of Allergy and Respiratory Medicine, Guy's Hospital, London, United Kingdom.
Abstract:
Adenovirus internalization generally has been accepted to involve an interaction of the adenoviral penton base protein with alpha(v)beta3 and alpha(v)beta5 cell surface integrins. In this study we show that exposure of a panel of melanoma cells to the beta1-activating antibody TS2/16 rendered such cells more susceptible to adenovirus infection. This increase in adenoviral infectivity paralleled effects on cell adhesion, and both these characteristics were mediated, in part, by the alpha5beta1 integrin. These observations suggest that alpha5beta1 may act as an alternative adenovirus receptor and that integrin-activating strategies may improve the efficacy of recombinant adenoviruses as vectors for gene therapy.
Insights
This study reveals that alpha5beta1 integrin can serve as an alternative receptor for adenovirus entry into cells. Activating this integrin may enhance adenovirus-based gene therapy vectors.
Area of Science:
- Cell Biology
- Virology
- Gene Therapy
Background:
- Adenovirus entry typically involves penton base interaction with alpha(v)beta3 and alpha(v)beta5 integrins.
- Integrins are crucial cell surface receptors mediating cell adhesion and signaling.
Purpose of the Study:
- To investigate the role of beta1 integrins in adenovirus infection.
- To explore alpha5beta1 integrin as a potential alternative adenovirus receptor.
- To assess the implications for gene therapy vector efficacy.
Main Methods:
- Melanoma cells were treated with a beta1-activating antibody (TS2/16).
- Adenovirus susceptibility and cell adhesion were measured.
- The involvement of alpha5beta1 integrin was analyzed.
Main Results:
- Activation of beta1 integrins increased melanoma cell susceptibility to adenovirus infection.
- This enhanced infectivity correlated with changes in cell adhesion.
- Alpha5beta1 integrin was identified as a mediator of these effects.
Conclusions:
- Alpha5beta1 integrin functions as an alternative receptor for adenovirus.
- Targeting integrin activation presents a strategy to improve recombinant adenovirus vector efficacy in gene therapy.