Evidence map›Paper›PMID 18495764›Full record

ArticleJournal of virology2008

Varicella-zoster virus open reading frame 66 protein kinase is required for efficient viral growth in primary human corneal stromal fibroblast cells.

Angela Erazo, Michael B Yee, Nikolaus Osterrieder, Paul R Kinchington

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 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 32 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 2 institutions in 1 country.

Angela ErazoDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Michael B Yee
Nikolaus Osterrieder
Paul R Kinchington
Cornell University · USUniversity of Pittsburgh · US

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
Immunology of Infectious DiseaseT32AI060525 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JoAnne L. Flynn · 2005 to 2026
$5.3M
VARICELLA ZOSTER VIRUS REGULATORY PROTEINSR01EY009397 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KINCHINGTON, PAUL R. · 1992 to 2005
$2.2M
VZV BACs: New Tools for Pathogenesis ResearchR21AI060843 · NIAID · CORNELL UNIVERSITY ITHACA · PI OSTERRIEDER, NIKOLAUS · 2004 to 2005
$370k
NEI NIH HHS EY08098NEI NIH HHS EY09397NEI NIH HHS P30 EY008098NEI NIH HHS R01 EY009397NIAID NIH HHS AI060843NIAID NIH HHS R21 AI060843NIAID NIH HHS T32 AI060525
6 · The paper itself

Abstract

Varicella-zoster virus (VZV) open reading frame 66 (ORF66) encodes a serine/threonine protein kinase that is not required for VZV growth in most cell types but is needed for efficient growth in T cells. The ORF66 kinase affects nuclear import and virion packaging of IE62, the major regulatory protein, and is known to regulate apoptosis in T cells. Here, we further examined the importance of ORF66 using VZV recombinants expressing green fluorescent protein (GFP)-tagged functional and kinase-negative ORF66 proteins. VZV virions with truncated or kinase-inactivated ORF66 protein were marginally reduced for growth and progeny yields in MRC-5 fibroblasts but were severely growth and replication impaired in low-passage primary human corneal stromal fibroblasts (PCF). To determine if the growth impairment was due to ORF66 kinase regulation of IE62 nuclear import, recombinant VZVs that expressed IE62 with alanine residues at S686, the suspected target by which ORF66 kinase blocks IE62 nuclear import, were made. IE62 S686A expressed by the VZV recombinant remained nuclear throughout infection and was not packaged into virions. However, the mutant virus still replicated efficiently in PCF cells. We also show that inactivation of the ORF66 kinase resulted in only marginally increased levels of apoptosis in PCF cells, which could not fully account for the cell-specific growth requirement of ORF66 kinase. Thus, the unique short region VZV kinase has important cell-type-specific functions that are separate from those affecting IE62 and apoptosis.

Indexed as

Virus ReplicationAmino Acid SubstitutionCell NucleusCells, CulturedFibroblastsGenes, ReporterGreen Fluorescent ProteinsHerpesvirus 3, HumanHumansImmediate-Early ProteinsMutagenesis, Site-DirectedProtein Serine-Threonine KinasesSequence DeletionStaining and LabelingTrans-ActivatorsViral Envelope ProteinsGreen Fluorescent ProteinsIE62 protein, Human herpesvirus 3Immediate-Early ProteinsProtein Serine-Threonine KinasesTrans-ActivatorsViral Envelope ProteinsViral Nonstructural Proteins

Identifiers

PMID18495764
PMCPMC2493351
OpenAlexW2112147962

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.