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 language | English |
|---|---|
| Journal | PLoS Pathogens |
| Volume | 3 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2007 Mar 1 |
Fingerprint
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 journal › Article
}
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 -