Human Adeno-Associated Virus Type 5 Is Only Distantly Related to Other Known Primate Helper-Dependent Parvoviruses

Bantel-Schaal, Ursula; Delius, Hajo; Schmidt, Rainer; zur Hausen, Harald

doi:10.1128/jvi.73.2.939-947.1999

Cited by 128Virus-based gene therapy researchParvovirus B19 Infection StudiesVirology and Viral Diseases

Human Adeno-Associated Virus Type 5 Is Only Distantly Related to Other Known Primate Helper-Dependent Parvoviruses

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Bantel-Schaal, Ursula, Delius, Hajo, Schmidt, Rainer, zur Hausen, Harald·1999·Journal of Virology

DOI 10.1128/jvi.73.2.939-947.1999PMC PMC103913

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Abstract

We have characterized 95% (4,404 nucleotides) of the genome of adeno-associated virus type 5 (AAV5), including part of the terminal repeats and the terminal resolution site. Our results show that AAV5 is different from all other described AAV serotypes at the nucleotide level and at the amino acid level. The sequence homology to AAV2, AAV3B, AAV4, and AAV6 at the nucleotide level is only between 54 and 56%. The positive strand contains two large open reading frames (ORFs). The left ORF encodes the nonstructural (Rep) proteins, and the right ORF encodes the structural (Cap) proteins. At the amino acid level the identities with the capsid proteins of other AAVs range between 51 and 59%, with a high degree of heterogeneity in regions which are considered to be on the exterior surface of the viral capsid. The overall identity for the nonstructural Rep proteins at the amino acid level is 54.4%. It is lowest at the C-terminal 128 amino acids (10%). There are only two instead of the common three putative Zn fingers in the Rep proteins. The Cap protein data suggest differences in capsid surfaces and raise the possibility of a host range distinct from those of other parvoviruses. This may have important implications for AAV vectors used in gene therapy.

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AAV5 has the most distinct sequence of the capsids (61.2% identity to AAV2; AAV8 83.6%; AAV9 82.7%).
“AAV5 has the most distinct sequence of the capsids (AAV5: 61.2% amino acid sequence identity to AAV2, AAV8: 83.6% amino acid sequence identity to AAV2, AAV9: 82.7% sequence identity to AAV2),55,56”
From Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates (2015) · cites this paper as [56]
The capsid-alignment results and Table 1 support that AAV5 is distinct from the serotypes this paper compared. But Table 1 gives 58.3% identity for AAV5 versus AAV2, not 61.2%, and the paper does not report the claimed AAV8 or AAV9 comparisons (page numbers unavailable in our copy). (LLM, conf=0.90)
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Recombinant Adeno-Associated Viral Vector Types 4 and 5: Preparation and Application for CNS Gene Transfer
Davidson, B. L., & Chiorini, J. A. (2003) · Humana Press eBooks · doi:10.1385/1-59259-304-6:269 · Cited by 8 · see citing works
Cloning of an Avian Adeno-Associated Virus (AAAV) and Generation of Recombinant AAAV Particles
Bossis, I., & Chiorini, J. A. (2003) · Journal of Virology · doi:10.1128/jvi.77.12.6799-6810.2003 · Cited by 93 · see citing works
Adeno-Associated Virus (AAV) Type 5 Rep Protein Cleaves a Unique Terminal Resolution Site Compared with Other AAV Serotypes
Chiorini, J. A., Afione, S. A., & Kotin, R. M. (1999) · Journal of Virology · doi:10.1128/jvi.73.5.4293-4298.1999 · Cited by 78 · see citing works

Authors: Bantel-Schaal, U., Delius, H., Schmidt, R., & zur Hausen, H.
Affiliations: Deutsches Krebsforschungszentrum Heidelberg, Forschungsschwerpunkt Angewandte Tumorvirologie F0400, D-69120 Heidelberg, Germany
German Cancer Research Center (DE)
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 1999-02
Volume: 73
Issue: 2
Pages: 939-947
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.73.2.939-947.1999
PMC: PMC103913
OpenAlex: W2119056879
Cited by: 128
References: 61
Citations by year: 2026: 2 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 6 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 1
FWCI: 5.28
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
PubMed Central (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords: AAV serotypes, sequence homology, capsid protein, Rep protein, zinc finger, terminal repeats, host range, gene therapy vectors, parvovirus
MeSH terms: Dependovirus, Amino Acid Sequence, Animals, Base Sequence, Capsid, DNA-Binding Proteins, DNA, Viral, HeLa Cells, Helper Viruses, Humans, Molecular Sequence Data, Primates, Viral Proteins, Genome, Viral, Sequence Homology, Amino Acid, Parvovirus

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Human Adeno-Associated Virus Type 5 Is Only Distantly Related to Other Known Primate Helper-Dependent Parvoviruses

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