The DOI matches its Crossref record; 192 of the 195 references it cites were found in a registry or an index.
AAV Capsid Structure and Cell Interactions
Abstract
The Adeno-associated viruses (AAVs) are not associated with any diseases, and their ability to package non-genomic DNA and to transduce different cell/tissue populations has generated significant interest in understanding their basic biology in efforts to improve their utilization for corrective gene delivery. This includes their capsid structure, cellular tropism and interactions for entry, uncoating, replication, DNA packaging, capsid assembly, and antibody neutralization. The human and nonhuman primate AAVs are clustered into serologically distinct genetic clade and serotype groups, which have distinct cellular/tissue tropisms and transduction efficiencies. These properties are highly dependent upon the AAV capsid amino acid sequence, their capsid structure, and their interactions with host cell factors, including cell surface receptors, co-receptors, signaling molecules, proteins involved in host DNA replication, and host-derived antibodies. This chapter reviews the current structural information on AAV capsids and the capsid viral protein regions playing a role in the cellular interactions conferring an infective phenotype, which are then used to annotate the functional regions of the capsid. Based on the current data, the indication is that the AAVs, like other members of the Parvoviridae and other ssDNA viruses that form a T = 1 capsid, have evolved a multifunctional capsid with conserved core regions as is required for efficient capsid trafficking, capsid assembly, and genome packaging. Disparate surface loop structures confer differential receptor recognition and are involved in antibody recognition. The role of structural regions in capsid uncoating remains to be elucidated.
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In the citing paper
“The unique topology of the AAV capsid confers cellular tropism by differential receptor binding.”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [18]
In the citing paper
“The first step of AAV transduction entails AAV binding to a primary receptor and co-receptor on the cell surface.18”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [18]
In the citing paper
“The AAV capsids have nine variable regions surrounded by conserved regions where the variable regions form loops and clusters on the exterior of the capsid.18–19”
From Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism (2016) · cites this paper as [18]
In the citing paper
“These protrusions are formed from interdigitating loops from two VPs and have the most extensive VP–VP interactions [23,24].”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [24]
In the citing paper
“This region has the least number of VP–VP interface interactions and represents the thinnest region of the virus capsid shell [23,24].”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [24]
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“The amino acid sequences and structural topology of these large outer loops have been reported to facilitate tissue tropism and transduction efficiency (Agbandje-McKenna & Kleinschmidt, 2011).”
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“They efficiently replicate in the presence of a helper virus, such as Adenovirus or Herpesvirus (2, 3), and have distinct capsid-governed tissue specificities and strict host ranges (4, 5).”
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“Eleven natural serotypes of AAVs have been identified so far, which have different capsid structures, resulting in differing tropism.(7) AAV tropism can also be further altered by creating recombinant versions of multiple AAV serotypes, a process known as pseudotyping.”
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“It is possible that VR-I is a dominant neutralizing epitope, due to proximity to unknown binding sites of one of the co-receptors (Agbandje-McKenna and Kleinschmidt, 2011) or other interactions important to trafficking in specific cells.”
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BackgroundSub-2 Å Ewald curvature corrected structure of an AAV2 capsid variant
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“The virions of these viruses are composed of nonenveloped capsids with T 1 icosahedral symmetry and diameters of 260 Å that enclose the ssDNA genome (4).”
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“In addition, various coreceptors, such as integrins and growth factor receptors, have been implicated in AAV infection in vitro (1, 23).”
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“This structural diversity arises primarily from the variable surface loops or regions (VRs) (6).”
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“The AAV T=1 icosahedral capsid is assembled using 60 subunits of the structural virus proteins (VPs) VP1,22, and 23, in an approximate ratio of 5:5:50 (29, 30).”
BackgroundMethodSelf-citationVirus-assisted directed evolution of enhanced suppressor tRNAs in mammalian cells
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Parvoviruses: Structure and Infection
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Structural Insights into Human Bocaparvoviruses
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“important for antigenic reactivity and infectivity in other parvoviruses and strainspecific antibody recognition for HBoV1 (30, 34, 48).”
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Precise Photoremovable Perturbation of a Virus–Host Interaction
Erickson, S. B., Mukherjee, R., Kelemen, R. E., Wrobel, C. J. J., Cao, X., & Chatterjee, A. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201700683 · Cited by 51
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Protease-activatable adeno-associated virus vector for gene delivery to damaged heart tissue
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Self-citationLi, C., Wu, S., Albright, B., Hirsch, M., Li, W., Tseng, Y.-S., Agbandje-McKenna, M., McPhee, S., Asokan, A., & Samulski, R. J. (2016) · Molecular Therapy · doi:10.1038/mt.2015.134 · Cited by 48
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“These viruses are composed of nonenveloped capsids with T 1 icosahedral symmetry and a diameter of 260 Å (1).”
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Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction
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“The surface protrusions and spikes surrounding the 3-fold axes are predominantly composed of the highly dynamic GH loop connecting the G and H strands within the capsid protein subunit (10, 11).”
BackgroundAn Emerging Adeno-Associated Viral Vector Pipeline for Cardiac Gene Therapy
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“A summary of current knowledge pertaining to the biology, preclinical studies, and clinical applications of the different AAV serotypes and pertinent literature has been reviewed elsewhere (Agbandje-McKenna and Kleinschmidt, 2011; Mingozzi and High, 2011).”
BackgroundEngineering AAV receptor footprints for gene therapy
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AAV-Mediated Gene Delivery to the Liver: Overview of Current Technologies and Methods
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“However, most rAAVs cannot cross the blood–brain barrier (BBB), and different rAAV stereotypes recognize different cell receptors and thus have different tropisms for distinct tissues and cell types (Agbandje-McKenna and Kleinschmidt, 2011; Wang et al., 2019), which causes difficulties in delivering rAAVs into the bra…”
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“various transduction efficiency in different host tissues (11).”
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“To date, 12 distinct human and nonhuman AAV serotypes (AAV1–12) have been described, and recombinant AAV (rAAV) vectors have been developed (Agbandje-McKenna and Kleinschmidt, 2011).”
Gene manipulation in liver ductal organoids by optimized recombinant adeno-associated virus vectors
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High-Throughput Dissection of AAV–Host Interactions: The Fast and the Curious
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Self-citationAdeno-associated virus and lentivirus vectors: a refined toolkit for the central nervous system
Blessing, D., & Déglon, N. (2016) · Current Opinion in Virology · doi:10.1016/j.coviro.2016.08.004 · Cited by 36
“They are responsible for surface topology and determine tropism and specificity [9].”
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Genome DNA leakage of Adeno–Associated virus under freeze–thaw stress
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Atomic structure of a rationally engineered gene delivery vector, AAV2. 5
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Self-citationComputationally guided AAV engineering for enhanced gene delivery
Guo, J., Lin, L. F., Oraskovich, S. V., de Jesús, J. A. R., Listgarten, J., & Schaffer, D. V. (2024) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2024.03.002 · Cited by 31
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“The nature of exposed amino acid residues on the capsid surface largely determines receptor attachment, tissue transduction, and antigenicity.(20) Therefore, the development of engineered AAV vectors designed either by rational modification of specific amino acids (rational mutagenesis) or in vitro/in vivo selection i…”
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AAV-8 Is More Efficient than AAV-9 in Transducing Neonatal Dog Heart
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“Future site-directed mutagenesis in these regions will help to pinpoint structural features that are responsible for the superior myocardial transduction by AAV-8 in newborn dogs.(28) It is currently unclear why AAV-9 can effectively transduce rodent heart but not newborn dog heart.”
Machine-learning-guided Directed Evolution for AAV Capsid Engineering
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Creating an arsenal of Adeno-associated virus (AAV) gene delivery stealth vehicles
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Self-citationReceptor Switching in Newly Evolved Adeno-associated Viruses
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Self-citation
Metadata
- Authors
- Agbandje-McKenna, M., & Kleinschmidt, J.
- Affiliations
- German Cancer Research Center (DE)
- Venue
- Methods in Molecular Biology
- Publisher
- Humana Press
- Published
- 2011-09-27
- Volume
- 807
- Pages
- 47-92
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- OpenAlex
- W124314106
- Cited by
- 215
- References
- 195
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 19 · 2023: 19 · 2022: 17 · 2021: 15 · 2020: 13 · 2019: 17 · 2018: 14 · 2017: 11 · 2016: 10 · 2015: 12 · 2014: 16 · 2013: 12 · 2012: 12
- FWCI
- 32.78
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- Locations
- Methods in molecular biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM082946)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- adeno-associated virus, capsid structure, capsid assembly, DNA packaging, cell tropism, receptor recognition, capsid uncoating, antibody neutralization, serotypes, gene delivery vectors, host cell interactions
- MeSH terms
- Dependovirus, Antibody Formation, Capsid, Humans, Models, Molecular, Endosomes, Viral Proteins, Protein Structure, Secondary
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