Evidence map›Paper›PMID 25056896›Full record

ArticleJournal of virology2014

Kaposi's sarcoma-associated herpesvirus ORF18 and ORF30 are essential for late gene expression during lytic replication.

Danyang Gong, Nicholas C Wu, Yafang Xie, Jun Feng, Leming Tong, Kevin F Brulois, Harding Luan, Yushen Du, Jae U Jung, Cun-yu Wang and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
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 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

34 citing papers in PubMed, 46 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

14 authors at 2 institutions in 1 country.

Danyang GongDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Nicholas C WuDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Yafang XieDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Jun FengDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Leming TongDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Kevin F BruloisDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Harding LuanDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Yushen DuDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA.
Jae U JungDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Cun-yu WangSchool of Dentistry, University of California, Los Angeles, California, USA.
Mo Kwan KangSchool of Dentistry, University of California, Los Angeles, California, USA.
No-Hee ParkSchool of Dentistry, University of California, Los Angeles, California, USA Department of Medicine, University of California, Los Angeles, California, USA.
Ren SunDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA rsun@mednet.ucla.edu twu@mednet.ucla.edu.
Ting-Ting WuDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, California, USA rsun@mednet.ucla.edu twu@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Southern California · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Roles of the K3 and K5 in KSHV Persistence and PathogenesisP01CA180779 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2013 to 2017
$7.3M
Reactivation of Kaposi's Sarcoma-Associated HerpesvirusR01CA091791 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SUN, REN · 2001 to 2017
$4.4M
KSHV RTA: more than viral replicationR01CA115284 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2005 to 2015
$3.1M
Role of Interleukin-6 in Gammaherpesvirus replicationR01DE015752 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SUN, REN · 2003 to 2007
$1.6M
Quantitative High-Resolution Genetic Profiling of a GammaherpesvirusR21AI078133 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SUN, REN · 2010 to 2011
$422k
NCI NIH HHS CA91791NCI NIH HHS P01 CA180779NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA091791NCI NIH HHS R01 CA115284NIAID NIH HHS AI078133NIAID NIH HHS R21 AI078133NIDCR NIH HHS DE15752NIDCR NIH HHS R01 DE015752
6 · The paper itself

Abstract

unlabelledKaposi's sarcoma-associated herpesvirus (KSHV) is associated with several human malignances. As saliva is likely the major vehicle for KSHV transmission, we studied in vitro KSHV infection of oral epithelial cells. Through infection of two types of oral epithelial cells, normal human oral keratinocytes (NHOKs) and papilloma-immortalized human oral keratinocyte (HOK16B) cells, we found that KSHV can undergo robust lytic replication in oral epithelial cells. By employing de novo lytic infection of HOK16B cells, we studied the functions of two previously uncharacterized genes, ORF18 and ORF30, during the KSHV lytic cycle. For this purpose, an ORF18-deficient virus and an ORF30-deficient virus were generated using a mutagenesis strategy based on bacterial artificial chromosome (BAC) technology. We found that neither ORF18 nor ORF30 is required for immediately early or early gene expression or viral DNA replication, but each is essential for late gene expression during both de novo lytic replication and reactivation. This critical role of ORF18 and ORF30 in late gene expression was also observed during KSHV reactivation. In addition, global analysis of viral transcripts by RNA sequencing indicated that ORF18 and ORF30 control the same set of viral genes. Therefore, we suggest that these two viral ORFs are involved in the same mechanism or pathway that coregulates the viral late genes as a group. IMPORTANCE: While KSHV can infect multiple cell types in vitro, only a few can support a full lytic replication cycle with progeny virions produced. Consequently, KSHV lytic replication is mostly studied through reactivation, which requires chemicals to induce the lytic cycle or overexpression of the viral transcriptional activator, RTA. In this study, we present a robust de novo lytic infection system based on oral epithelial cells. Using this system, we demonstrate the role of two viral ORFs, ORF18 and ORF30, in regulating viral gene expression during KSHV lytic replication. As the major route of KSHV transmission is thought to be via saliva, this new KSHV lytic replication system will have important utility in the field.

Indexed as

Gene Expression Regulation, ViralOpen Reading FramesBase SequenceCell LineChromosomes, Artificial, BacterialHerpesvirus 8, HumanHigh-Throughput Nucleotide SequencingHumansKeratinocytesMolecular Sequence DataMouth MucosaSequence DeletionSignal TransductionViral ProteinsVirus ActivationVirus ReplicationViral Proteins

Identifiers

PMID25056896
PMCPMC4178812
OpenAlexW2089425368

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.