Evidence map›Paper›PMID 18463148›Full record

ArticleJournal of virology2008

Development of cell lines that provide tightly controlled temporal translation of the human cytomegalovirus IE2 proteins for complementation and functional analyses of growth-impaired and nonviable IE2 mutant viruses.

Rebecca L Sanders, Charles L Clark, Christopher S Morello, Deborah H Spector

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 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

19 citing papers in PubMed, 27 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 1 institution in 1 country.

Rebecca L SandersDepartment of Cellular and Molecular Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0712, USA.
Charles L Clark
Christopher S Morello
Deborah H Spector
University of California, San Diego · US

Funding

Human Cytomegalovirus Gene ExpressionR01CA034729 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SPECTOR, DEBORAH HYE · 1985 to 2011
$4.8M
DYSREGULATION OF THE CELL CYCLE BY HUMAN CYTOMEGALOVIRUSR01CA073490 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SPECTOR, DEBORAH HYE · 1998 to 2007
$2.8M
NCI NIH HHS CA034729NCI NIH HHS CA073490NCI NIH HHS R01 CA034729NCI NIH HHS R01 CA073490
6 · The paper itself

Abstract

The human cytomegalovirus (HCMV) IE2 86 protein is essential for viral replication. Two other proteins, IE2 60 and IE2 40, which arise from the C-terminal half of IE2 86, are important for later stages of the infection. Functional analyses of IE2 86 in the context of the infection have utilized bacterial artificial chromosomes as vectors to generate mutant viruses. One limitation is that many mutations result in debilitated or nonviable viruses. Here, we describe a novel system that allows tightly controlled temporal expression of the IE2 proteins and provides complementation of both growth-impaired and nonviable IE2 mutant viruses. The strategy involves creation of cell lines with separate lentiviruses expressing a bicistronic RNA with a selectable marker as the first open reading frame (ORF) and IE2 86, IE2 60, or IE2 40 as the second ORF. Induction of expression of the IE2 proteins occurs only following DNA recombination events mediated by Cre and FLP recombinases that delete the first ORF. HCMV encodes Cre and FLP, which are expressed at immediate-early (for IE2 86) and early-late (for IE2 40 and IE2 60) times, respectively. We show that the presence of full-length IE2 86 alone provides some complementation for virus production, but the correct temporal expression of IE2 86 and IE2 40 together has the most beneficial effect for early-late gene expression and synthesis of infectious virus. This approach for inducible protein translation can be used for complementation of other mutations as well as controlled expression of toxic cellular and microbial proteins.

Indexed as

Cell LineCytomegalovirusGene DeletionGene ExpressionGenetic Complementation TestHumansImmediate-Early ProteinsProtein BiosynthesisRecombination, GeneticTime FactorsTrans-ActivatorsVirologyVirus ReplicationIE2 protein, CytomegalovirusImmediate-Early ProteinsTrans-Activators

Identifiers

PMID18463148
PMCPMC2446980
OpenAlexW2142217082

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.