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Cited by 24Virus-based gene therapy researchRNA Interference and Gene DeliveryViral Infectious Diseases and Gene Expression in Insects

The function of DNA binding protein nucleophosmin in AAV replication

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Satkunanathan, Stifani, Thorpe, Robin, Zhao, Yuan·2017·Virology
DOI 10.1016/j.virol.2017.07.007PMC PMC5572047
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Abstract

Adeno-associated viruses (AAV) contain minimal viral proteins necessary for their replication. During virus assembly, AAV acquire, inherently and submissively, various cellular proteins. Our previous studies identified the association of AAV vectors with the DNA binding protein nucleophosmin (NPM1). Nucleophosmin has been reported to enhance AAV infection by mobilizing AAV capsids into and out of the nucleolus, indicating the importance of NPM1 in the AAV life cycle; however the role of NPM1 in AAV production remains unknown. In this study, we systematically investigated NPM1 function on AAV production using NPM1 knockdown cells and revealing for the first time the presence of G-quadruplex DNA sequences (GQRS) in the AAV genome, the synergistic NPM1-GQRS function in AAV production and the significant enhancement of NPM1 gene knockdown on AAV vector production. Understanding the role of cellular proteins in the AAV life cycle will greatly facilitate high titre production of AAV vectors for clinical use.

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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 [14]

    The Introduction (page unavailable) says DNA-binding proteins interact with the AAV ITR, and the Results section on NPM1 interaction with AAV DNA reports NPM1 binding to an ITR sequence. The passages do not say that the ITR stimulates antiviral or DNA-damage response pathways; searches for those responses found no supporting passage. (LLM, conf=0.86)

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Cited by

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Authors
Satkunanathan, S., Thorpe, R., & Zhao, Y.
Affiliations
National Institute for Biological Standards and Control (GB)
Corresponding author
Zhao, Yuan
ORCID
Zhao, Yuan
Venue
Virology
Publisher
Elsevier BV
Published
2017-10
Volume
510
Pages
46-54
ISSN
0042-6822 (ISSN-L)
DOI
10.1016/j.virol.2017.07.007
PMC
PMC5572047
OpenAlex
W2736192666
Cited by
24
References
4
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2
FWCI
1.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Virology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Department of Health
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 › Viral Infectious Diseases and Gene Expression in Insects
Keywords
adeno-associated virus, nucleophosmin, NPM1, AAV vector production, G-quadruplex, viral genome, nucleolus, viral life cycle, gene knockdown
MeSH terms
Nucleophosmin, Dependovirus, Cell Line, DNA-Binding Proteins, DNA, Viral, Humans, Nuclear Proteins, Virus Replication, G-Quadruplexes, Host-Pathogen Interactions, Gene Knockdown Techniques

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