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.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Yu F,Harada JN,Brown HJ,Deng H,Song MJ,Wu TT,Kato-Stankiewicz J,Nelson CG,Vieira J,Tamanoi F,Chanda SK,Sun Rdoi
10.1371/journal.ppat.0030044subject
Has Abstractpub_date
2007-03-01 00:00:00pages
e44issue
3eissn
1553-7366issn
1553-7374pii
06-PLPA-RA-0231R3journal_volume
3pub_type
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