Evidence map›Paper›PMID 18463154›Full record

ArticleJournal of virology2008

Recombinant adeno-associated viral vectors are deficient in provoking a DNA damage response.

Michalis Fragkos, Madlaina Breuleux, Nathalie Clément, Peter Beard

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 42 citations in OpenAlex.

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  15. Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
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  17. Review
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  19. Parvovirus diversity and DNA damage responses.Cold Spring Harbor perspectives in biology · 2013
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 2 countries.

Michalis FragkosSwiss Institute for Experimental Cancer Research, EPFL SV ISREC, Chemin des Boveresses 155, Case postale, CH-1066 Epalinges, Switzerland.
Madlaina Breuleux
Nathalie Clément
Peter Beard
École Polytechnique Fédérale de Lausanne · CHIcahn School of Medicine at Mount Sinai · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adeno-associated virus type 2 (AAV2) provokes a DNA damage response that mimics a stalled replication fork. We have previously shown that this response is dependent on ataxia telangiectasia-mutated and Rad3-related kinase and involves recruitment of DNA repair proteins into foci associated with AAV2 DNA. Here, we investigated whether recombinant AAV2 (rAAV2) vectors are able to produce a similar response. Surprisingly, the results show that both single-stranded and double-stranded green fluorescent protein-expressing rAAV2 vectors are defective in producing such a response. We show that the DNA damage signaling initiated by AAV2 was not due to the virus-encoded Rep or viral capsid proteins. UV-inactivated AAV2 induced a response similar to that of untreated AAV2. This type of DNA damage response was not provoked by other DNA molecules, such as single-stranded bacteriophage M13 or plasmid DNAs. Rather, the results indicate that the ability of AAV2 to produce a DNA damage response can be attributed to the presence of cis-acting AAV2 DNA sequences, which are absent in rAAV2 vectors and could function as origins of replication creating stalled replication complexes. This hypothesis was tested by using a single-stranded rAAV2 vector containing the p5 AAV2 sequence that has previously been shown to enhance AAV2 replication. This vector was indeed able to trigger DNA damage signaling. These findings support the conclusion that efficient formation of AAV2 replication complexes is required for this AAV2-induced DNA damage response and provide an explanation for the poor response in rAAV2-infected cells.

Indexed as

DNA DamageCell LineDependovirusDNA, ViralGenes, ReporterGenetic VectorsGreen Fluorescent ProteinsHumansUltraviolet RaysVirus ReplicationDNA, ViralGreen Fluorescent Proteins

Identifiers

PMID18463154
PMCPMC2493315
OpenAlexW2169327072

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.