AlphaVbeta5 integrin: a co-receptor for adeno-associated virus type 2 infection

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Updated: Jul 6, 2026

A Quantitative Dot Blot Assay for AAV Titration and Its Use for Functional Assessment of the Adeno-associated Virus Assembly-activating Proteins
14:49

A Quantitative Dot Blot Assay for AAV Titration and Its Use for Functional Assessment of the Adeno-associated Virus Assembly-activating Proteins

Published on: June 12, 2018

C Summerford1, J S Bartlett, R J Samulski

  • 1Gene Therapy Center, Department of Pharmacology, University of North Carolina at Chapel Hill, 27599, USA.

Nature Medicine
|January 12, 1999
PubMed

Insights

Adeno-associated virus type 2 (AAV-2) uses alphaVbeta5 integrin as a co-receptor to facilitate viral entry. This finding impacts gene therapy strategies using AAV vectors for efficient gene delivery.

Area of Science:

  • Virology
  • Molecular Biology
  • Gene Therapy

Background:

  • Viral entry mechanisms are crucial for understanding pathogen infection and developing viral vectors for gene delivery.
  • Adenovirus and HSV utilize a two-step entry process involving primary receptors and co-receptors.
  • Heparan sulfate proteoglycan is a known primary attachment receptor for adeno-associated virus type 2 (AAV-2).

Purpose of the Study:

  • To investigate the role of alphaVbeta5 integrin in adeno-associated virus type 2 (AAV-2) infection.
  • To determine if alphaVbeta5 integrin acts as a primary attachment receptor or a co-receptor for AAV-2.
  • To assess the implications of alphaVbeta5 integrin's function on AAV-based gene therapy vectors.

Main Methods:

  • Utilized the chelating agent EDTA to assess integrin function's impact on AAV infection.
  • Performed viral overlay experiments on purified plasma membrane proteins and immunoprecipitated integrin beta5 subunit.
  • Conducted viral binding and internalization studies using genetically defined cells expressing alphaVbeta5 integrin.

Main Results:

  • EDTA treatment decreased AAV infection, suggesting integrin-mediated entry.
  • AAV-2 was found to directly associate with the beta5 subunit of alphaVbeta5 integrin.
  • Cells expressing alphaVbeta5 integrin showed increased susceptibility to AAV infection.
  • AlphaVbeta5 integrin functions as a co-receptor, facilitating AAV-2 internalization rather than initial attachment.

Conclusions:

  • AlphaVbeta5 integrin is essential for efficient AAV-2 infection, acting as a co-receptor.
  • The direct association and internalization role of alphaVbeta5 integrin have significant implications for AAV vector design in gene therapy.
  • Understanding AAV-2 co-receptor interactions enhances the potential for targeted and effective gene delivery systems.

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