Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus

Fuqu Yu, Josephine N. Harada, Helen J. Brown, Hongyu Deng, Moon Jung Song, Ting Ting Wu, Juran Kato-Stankiewicz, Christian G. Nelson, Jeffrey Vieira, Fuyuhiko Tamanoi, Sumit K. Chanda, Ren Sun

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.

Original languageEnglish
JournalPLoS Pathogens
Volume3
Issue number3
DOIs
Publication statusPublished - 2007 Mar 1

Fingerprint

Human Herpesvirus 8
Herpesviridae
Life Cycle Stages
Primary Effusion Lymphoma
Viruses
Virology
Viral Genes
Viral Genome
Mitogen-Activated Protein Kinase Kinases
Complementary DNA
Gene Expression
Population
Proteins
Therapeutics

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus. / Yu, Fuqu; Harada, Josephine N.; Brown, Helen J.; Deng, Hongyu; Song, Moon Jung; Wu, Ting Ting; Kato-Stankiewicz, Juran; Nelson, Christian G.; Vieira, Jeffrey; Tamanoi, Fuyuhiko; Chanda, Sumit K.; Sun, Ren.

In: PLoS Pathogens, Vol. 3, No. 3, 01.03.2007.

Research output: Contribution to journalArticle

Yu, F, Harada, JN, Brown, HJ, Deng, H, Song, MJ, Wu, TT, Kato-Stankiewicz, J, Nelson, CG, Vieira, J, Tamanoi, F, Chanda, SK & Sun, R 2007, 'Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus', PLoS Pathogens, vol. 3, no. 3. https://doi.org/10.1371/journal.ppat.0030044
Yu, Fuqu ; Harada, Josephine N. ; Brown, Helen J. ; Deng, Hongyu ; Song, Moon Jung ; Wu, Ting Ting ; Kato-Stankiewicz, Juran ; Nelson, Christian G. ; Vieira, Jeffrey ; Tamanoi, Fuyuhiko ; Chanda, Sumit K. ; Sun, Ren. / Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus. In: PLoS Pathogens. 2007 ; Vol. 3, No. 3.
@article{217f7580de15432e962f4fc65c41b91f,
title = "Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus",
abstract = "The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.",
author = "Fuqu Yu and Harada, {Josephine N.} and Brown, {Helen J.} and Hongyu Deng and Song, {Moon Jung} and Wu, {Ting Ting} and Juran Kato-Stankiewicz and Nelson, {Christian G.} and Jeffrey Vieira and Fuyuhiko Tamanoi and Chanda, {Sumit K.} and Ren Sun",
year = "2007",
month = "3",
day = "1",
doi = "10.1371/journal.ppat.0030044",
language = "English",
volume = "3",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus

AU - Yu, Fuqu

AU - Harada, Josephine N.

AU - Brown, Helen J.

AU - Deng, Hongyu

AU - Song, Moon Jung

AU - Wu, Ting Ting

AU - Kato-Stankiewicz, Juran

AU - Nelson, Christian G.

AU - Vieira, Jeffrey

AU - Tamanoi, Fuyuhiko

AU - Chanda, Sumit K.

AU - Sun, Ren

PY - 2007/3/1

Y1 - 2007/3/1

N2 - The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.

AB - The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.

UR - http://www.scopus.com/inward/record.url?scp=34047204739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047204739&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.0030044

DO - 10.1371/journal.ppat.0030044

M3 - Article

C2 - 17397260

AN - SCOPUS:34047204739

VL - 3

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 3

ER -