» Articles » PMID: 34711462

Adeno-associated Virus (AAV) Cell Entry: Structural Insights

Overview
Date 2021 Oct 29
PMID 34711462
Citations 44
Authors
Affiliations
Soon will be listed here.
Abstract

Adeno-associated virus (AAV) is the leading vector in emerging treatments of inherited diseases. Higher transduction efficiencies and cellular specificity are required for broader clinical application, motivating investigations of virus-host molecular interactions during cell entry. High-throughput methods are identifying host proteins more comprehensively, with subsequent molecular studies revealing unanticipated complexity and serotype specificity. Cryogenic electron microscopy (cryo-EM) provides a path towards structural details of these sometimes heterogeneous virus-host complexes, and is poised to illuminate more fully the steps in entry. Here presented, is progress in understanding the distinct steps of glycan attachment, and receptor-mediated entry/trafficking. Comparison with structures of antibody complexes provides new insights on immune neutralization with implications for the design of improved gene therapy vectors.

Citing Articles

AAV-based vectors for human diseases modeling in laboratory animals.

Aliev T, Yudkin D Front Med (Lausanne). 2025; 11:1499605.

PMID: 40007819 PMC: 11859266. DOI: 10.3389/fmed.2024.1499605.


Double-strand break repair pathways differentially affect processing and transduction by dual AAV vectors.

Maurer A, Benyamini B, Whitney O, Fan V, Cattoglio C, Kissiov D Nat Commun. 2025; 16(1):1532.

PMID: 39934106 PMC: 11814140. DOI: 10.1038/s41467-025-56738-5.


AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.

Kim J, Kurial S, Choksi P, Nunez M, Lunow-Luke T, Bartel J Nat Biotechnol. 2025; .

PMID: 39881029 DOI: 10.1038/s41587-024-02523-6.


Challenges in Humoral Immune Response to Adeno-Associated Viruses Determination.

Naumova D, Krokunova T, Maksimov D, Mityaeva O, Astakhova E, Volchkov P Int J Mol Sci. 2025; 26(2).

PMID: 39859531 PMC: 11765838. DOI: 10.3390/ijms26020816.


Advances in Gene Therapy for Rare Diseases: Targeting Functional Haploinsufficiency Through AAV and mRNA Approaches.

Bara-Ledesma N, Viteri-Noel A, Lopez Rodriguez M, Stamatakis K, Fabregate M, Vazquez-Santos A Int J Mol Sci. 2025; 26(2).

PMID: 39859294 PMC: 11765483. DOI: 10.3390/ijms26020578.


References
1.
Tseng Y, Gurda B, Chipman P, McKenna R, Afione S, Chiorini J . Adeno-associated virus serotype 1 (AAV1)- and AAV5-antibody complex structures reveal evolutionary commonalities in parvovirus antigenic reactivity. J Virol. 2014; 89(3):1794-808. PMC: 4300747. DOI: 10.1128/JVI.02710-14. View

2.
Mizukami H, Young N, Brown K . Adeno-associated virus type 2 binds to a 150-kilodalton cell membrane glycoprotein. Virology. 1996; 217(1):124-30. DOI: 10.1006/viro.1996.0099. View

3.
Zhang F, Aguilera J, Beaudet J, Xie Q, Lerch T, Davulcu O . Characterization of interactions between heparin/glycosaminoglycan and adeno-associated virus. Biochemistry. 2013; 52(36):6275-85. PMC: 3859860. DOI: 10.1021/bi4008676. View

4.
Poon M, Tsang W, Chan S, Li H, Ng H, Waye M . Dyslexia-associated kiaa0319-like protein interacts with axon guidance receptor nogo receptor 1. Cell Mol Neurobiol. 2010; 31(1):27-35. PMC: 11498553. DOI: 10.1007/s10571-010-9549-1. View

5.
Xie Q, Spilman M, Meyer N, Lerch T, Stagg S, Chapman M . Electron microscopy analysis of a disaccharide analog complex reveals receptor interactions of adeno-associated virus. J Struct Biol. 2013; 184(2):129-35. PMC: 3866096. DOI: 10.1016/j.jsb.2013.09.004. View