Evidence map›Paper›PMID 24335317›Full record

ArticleJournal of virology2014

Highly divergent integration profile of adeno-associated virus serotype 5 revealed by high-throughput sequencing.

Tyler Janovitz, Thiago Oliveira, Michel Sadelain, Erik Falck-Pedersen

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 24% 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

7 citing papers in PubMed, 21 citations in OpenAlex.

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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 3 institutions in 1 country.

Tyler JanovitzTri-Institutional MD-PhD Program, Weill Medical College of Cornell University, New York, New York, USA.
Thiago Oliveira
Michel Sadelain
Erik Falck-Pedersen
Memorial Sloan Kettering Cancer Center · USCornell University · USRockefeller University · US

Funding

Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
Regulation of host cell inflammatory and maturation response through AdV DNAdeteR01AI094050 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI FALCK-PEDERSEN, ERIK S · 2011 to 2015
$2.1M
NIAID NIH HHS R01 AI094050NIGMS NIH HHS T32 GM007739NIGMS NIH HHS T32GM07739
6 · The paper itself

Abstract

unlabelledAdeno-associated virus serotype 5 (AAV-5) is a human parvovirus that infects a high percentage of the population. It is the most divergent AAV, the DNA sequence cleaved by the viral endonuclease is distinct from all other described serotypes and, uniquely, AAV-5 does not cross-complement the replication of other serotypes. In contrast to the well-characterized integration of AAV-2, no published studies have investigated the genomic integration of AAV-5. In this study, we analyzed more than 660,000 AAV-5 integration junctions using high-throughput integrant capture sequencing of infected human cells. The integration activity of AAV-5 was 99.7% distinct from AAV-2 and favored intronic sequences. Genome-wide integration was highly correlated with viral replication protein binding and endonuclease sites, and a 39-bp consensus integration motif was revealed that included these features. Algorithmic scanning identified 126 AAV-5 hot spots, the largest of which encompassed 3.3% of all integration events. The unique aspects of AAV-5 integration may provide novel tools for biotechnology and gene therapy. IMPORTANCE: Viral integration into the host genome is an important aspect of virus host cell biology. Genomic integration studies of the small single-stranded AAVs have largely focused on site preferential integration of AAV-2, which depends on the viral replication protein (Rep). We have now established the first genome wide integration profile of the highly divergent AAV-5 serotype. Using integrant capture sequencing, more than 600,000 AAV-5 integration junctions in human cells were analyzed. AAV-5 integration hot spots were 99.7% distinct from AAV-2. Integration favored intronic sequences, occurred on all chromosomes, and integration hot spot distribution was correlated with human genomic GAGC repeats and transcriptional activity. These features support expansion of AAV-5 based vectors for gene transfer considerations.

Indexed as

Virus IntegrationBase SequenceBinding SitesCell LineChromosome MappingConsensus SequenceDependovirusDNA-Binding ProteinsEndonucleasesGene OrderGenome, ViralHigh-Throughput Nucleotide SequencingHumansNucleotide MotifsPosition-Specific Scoring MatricesViral ProteinsDNA-Binding ProteinsEndonucleasesViral Proteins

Identifiers

PMID24335317
PMCPMC3958079
OpenAlexW2149433604

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.