Evidence map›Paper›PMID 18057257›Full record

ArticleJournal of virology2008

Complete in vitro reconstitution of adeno-associated virus DNA replication requires the minichromosome maintenance complex proteins.

Kevin Nash, Weijun Chen, Nicholas Muzyczka

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 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

36 citing papers in PubMed, 66 citations in OpenAlex.

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  18. AAV's Golden Jubilee.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    Article
  19. Vaccinia virus as a subhelper for AAV replication and packaging.Molecular therapy. Methods & clinical development · 2015
    Article
  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

3 authors at 2 institutions in 1 country.

Kevin NashDepartment of Molecular Genetics and Microbiology, University of Florida, 1376 Mowry Rd., Gainesville, FL 32610, USA. nash@ufl.edu
Weijun Chen
Nicholas Muzyczka
University of Florida · USFlorida College · US

Funding

VIRAL VECTOR DELIVERY OF ANTISENSE TO ACE MRNA IN CARDIOVASCULAR DISEASEP01HL059412 · NHLBI · UNIVERSITY OF FLORIDA · PI MUZYCZKA, NICHOLAS · 1998 to 2012
$20.2M
NHLBI NIH HHS P01 HL059412NHLBI NIH HHS P01 HL59412
6 · The paper itself

Abstract

Adeno-associated virus (AAV) replicates its DNA exclusively by a leading-strand DNA replication mechanism and requires coinfection with a helper virus, such as adenovirus, to achieve a productive infection. In previous work, we described an in vitro AAV replication assay that required the AAV terminal repeats (the origins for DNA replication), the AAV Rep protein (the origin binding protein), and an adenovirus-infected crude extract. Fractionation of these crude extracts identified replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and polymerase delta as cellular enzymes that were essential for AAV DNA replication in vitro. Here we identify the remaining factor that is necessary as the minichromosome maintenance (MCM) complex, a cellular helicase complex that is believed to be the replicative helicase for eukaryotic chromosomes. Thus, polymerase delta, RFC, PCNA, and the MCM complex, along with the virally encoded Rep protein, constitute the minimal protein complexes required to reconstitute efficient AAV DNA replication in vitro. Interfering RNAs targeted to MCM and polymerase delta inhibited AAV DNA replication in vivo, suggesting that one or more components of the MCM complex and polymerase delta play an essential role in AAV DNA replication in vivo as well as in vitro. Our reconstituted in vitro DNA replication system is consistent with the current genetic information about AAV DNA replication. The use of highly conserved cellular replication enzymes may explain why AAV is capable of productive infection in a wide variety of species with several different families of helper viruses.

Indexed as

Cell FractionationComplex MixturesDependovirusDNA HelicasesDNA ReplicationDNA, ViralGene SilencingIn Vitro TechniquesComplex MixturesDNA HelicasesDNA, Viral

Identifiers

PMID18057257
PMCPMC2224442
OpenAlexW2070511876

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.