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Cited by 13Virus-based gene therapy researchRNA Interference and Gene DeliveryGenomics and Chromatin Dynamics

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RFX1 and RFX3 Transcription Factors Interact with the D Sequence of Adeno-Associated Virus Inverted Terminal Repeat and Regulate AAV Transduction

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Julien, Laura, Chassagne, Julie, Peccate, Cécile, Lorain, Stéphanie, Piétri-Rouxel, France, Danos, Olivier, Benkhelifa-Ziyyat, Sofia·2018·Scientific Reports
DOI 10.1038/s41598-017-18604-3PMC PMC5760533
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Abstract

Adeno-associated virus (AAV) transduction efficiency depends on the way in which cellular proteins process viral genomes in the nucleus. In this study, we have investigated the binding of nuclear proteins to the double stranded D (dsD) sequence of the AAV inverted terminal repeat (ITRs) by electromobility shift assay. We present here several lines of evidence that transcription factors belonging to the RFX protein family bind specifically and selectively to AAV2 and AAV1 dsD sequences. Using supershift experiments, we characterize complexes containing RFX1 homodimers and RFX1/RFX3 heterodimers. Following transduction of HEK-293 cells, the AAV genome can be pulled-down by RFX1 and RFX3 antibodies. Moreover, our data suggest that RFX proteins which interact with transcriptional enhancers of several mammalian DNA viruses, can act as regulators of AAV mediated transgene expression.

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  • The AAV ITR interacts with host proteins and can stimulate anti-viral and DNA damage response pathways.

    “it is known that the AAV ITR interacts with a number of host proteins and can stimulate anti-viral and DNA damage response pathways.12–16”

    From Adeno-Associated Virus Serotype-Specific Inverted Terminal Repeat Sequence Role in Vector Transgene Expression (2020) · cites this paper as [12]

    The Introduction (page unavailable) says that several host proteins bind the AAV ITR, including proteins active in double-strand break repair. It does not say that the ITR stimulates antiviral or DNA damage response pathways; the repair proteins are described as recognizing and processing the ITR instead. (LLM, conf=0.84)

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Metadata

Authors
Julien, L., Chassagne, J., Peccate, C., Lorain, S., Piétri-Rouxel, F., Danos, O., & Benkhelifa-Ziyyat, S.
Affiliations
  • Inserm (FR)
  • Hôpital Necker-Enfants Malades (FR)
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-01-09
Volume
8
Issue
1
Pages
210-210
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-017-18604-3
PMC
PMC5760533
OpenAlex
W2781493226
Cited by
13
References
5
Citations by year
2026: 2 · 2024: 1 · 2022: 3 · 2020: 5 · 2018: 2
FWCI
1.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • University of Pennsylvania (p0001)
  • Institut National de la Santé et de la Recherche Médicale
  • Université Pierre et Marie Curie
  • Université de Genève
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
RFX1, RFX3, adeno-associated virus, inverted terminal repeats, d-sequences, transcription factors, protein-DNA interactions, AAV2, AAV1, viral transduction efficiency, transgene expression regulation, nuclear protein binding
MeSH terms
Regulatory Factor X Transcription Factors, Regulatory Factor X1, Dependovirus, Humans, Protein Binding, Transduction, Genetic, Terminal Repeat Sequences, HEK293 Cells

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