DNA-Binding Activity of Adeno-Associated Virus Rep Is Required for Inverted Terminal Repeat-Dependent Complex Formation with Herpes Simplex Virus ICP8
Open accessAbstract
Herpes simplex virus (HSV) helper functions for (AAV) replication comprise HSV ICP8 and helicase-primase UL5/UL52/UL8. Here we show that N-terminal amino acids of AAV Rep78 that contact the Rep-binding site within the AAV inverted terminal repeat (ITR) are required for ternary-complex formation with infected-cell protein 8 (ICP8) on AAV single-strand DNA (ssDNA) in vitro and for colocalization in nuclear replication domains in vivo. Our data suggest that HSV-dependent AAV replication is initiated by Rep contacting the AAV ITR and by cooperative binding of ICP8 on AAV ssDNA.
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Single-stranded binding proteins E2A (adenovirus) or ICP8 (herpes virus) provided by helper viruses are involved in displacement of the ssDNA genome.
“In that process, the single-stranded binding proteins, E2A (adenovirus) or ICP8 (herpes virus) provided by the helper viruses are involved [2, 51].”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [51]
During AAV replication, the N-terminus of the large Rep proteins binds specifically to the RBE within the ITRs and cleaves the trs, which allows self-priming and induces further replication.
“During AAV replication, the N-terminus of the large Rep proteins (Table 2 & Figure 6A) [51] bind specifically to the RBE within the ITRs and cleave the trs [52] which allows self-priming and induces further replication.”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [51]
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Basic Biology of Adeno-Associated Virus (AAV) Vectors Used in Gene Therapy
Balakrishnan, B., & Jayandharan, G. (2014) · Current Gene Therapy · doi:10.2174/1566523214666140302193709 · Cited by 225 · see citing works
Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses
Bennett, A., Mietzsch, M., & Agbandje-McKenna, M. (2017) · Future Virology · doi:10.2217/fvl-2017-0011 · Cited by 82 · see citing works
Self-citation
- Authors
- Alex, M., Weger, S., Mietzsch, M., Slanina, H., Cathomen, T., & Heilbronn, R.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Medizinische Hochschule Hannover (DE)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2012-03
- Volume
- 86
- Issue
- 5
- Pages
- 2859-2863
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC3302247
- OpenAlex
- W2023014790
- Cited by
- 9
- References
- 0
- Citations by year
- 2023: 1 · 2021: 3 · 2018: 1 · 2017: 1 · 2014: 2 · 2013: 1
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Infectious Diseases › Parvovirus B19 Infection Studies
- Keywords
- adeno-associated virus, inverted terminal repeats, DNA-binding activity, ternary complex formation, single-stranded DNA
- MeSH terms
- Dependovirus, Binding Sites, DNA Replication, DNA Helicases, DNA-Binding Proteins, HeLa Cells, Helper Viruses, Humans, Parvoviridae Infections, Viral Proteins, Virus Replication, Protein Structure, Tertiary, Simplexvirus, Terminal Repeat Sequences, Protein Transport
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