NF-kappaB serves as a cellular sensor of Kaposi's sarcoma-associated herpesvirus latency and negatively regulates K-Rta by antagonizing the RBP-Jkappa coactivator
| Autor: | Izumiya, Yoshihiro, Izumiya, Chie, Hsia, Datsun, Ellison, Thomas J, Luciw, Paul A, Kung, Hsing-Jien |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Gene Expression Regulation
Viral viruses Down-Regulation biochemical phenomena metabolism and nutrition genetics metabolism [Herpesvirus 8 Human] metabolism [Trans-Activators] Cell Line Virus Latency antagonists & inhibitors metabolism [Immunoglobulin J Recombination Signal Sequence-Binding Protein] genetics [Promoter Regions Genetic] Medicine and Health Sciences Humans metabolism [NF-kappa B] Virus Activation metabolism [Immediate-Early Proteins] |
| Zdroj: | Izumiya, Yoshihiro; Izumiya, Chie; Hsia, Datsun; Ellison, Thomas J; Luciw, Paul A; & Kung, Hsing-Jien. (2009). NF-kappaB serves as a cellular sensor of Kaposi's sarcoma-associated herpesvirus latency and negatively regulates K-Rta by antagonizing the RBP-Jkappa coactivator.. Journal of virology, 83(9), 4435-4446. UC Office of the President: California HIV/AIDS Research Program. Retrieved from: http://www.escholarship.org/uc/item/06w534p7 |
| Popis: | Successful viral replication is dependent on a conducive cellular environment; thus, viruses must be sensitive to the state of their host cells. We examined the idea that an interplay between viral and cellular regulatory factors determines the switch from Kaposi's sarcoma-associated herpesvirus (KSHV) latency to lytic replication. The immediate-early gene product K-Rta is the first viral protein expressed and an essential factor in reactivation; accordingly, this viral protein is in a key position to serve as a viral sensor of cellular physiology. Our approach aimed to define a host transcription factor, i.e., host sensor, which modulates K-Rta activity on viral promoters. To this end, we developed a panel of reporter plasmids containing all 83 putative viral promoters for a comprehensive survey of the response to both K-Rta and cellular transcription factors. Interestingly, members of the NF-kappaB family were shown to be strong negative regulators of K-Rta transactivation for all but two viral promoters (Ori-RNA and K12). Recruitment of K-Rta to the ORF57 and K-bZIP promoters, but not the K12 promoter, was significantly impaired when NF-kappaB expression was induced. Many K-Rta-responsive promoters modulated by NF-kappaB contain the sequence of the RBP-Jkappa binding site, a major coactivator which anchors K-Rta to target promoters via consensus motifs which overlap with that of NF-kappaB. Gel shift assays demonstrated that NF-kappaB inhibits the binding of RBP-Jkappa and forms a complex with RBP-Jkappa. Our results support a model in which a balance between K-Rta/RBP-Jkappa and NF-kappaB activities determines KSHV reactivation. An important feature of this model is that the interplay between RBP-Jkappa and NF-kappaB on viral promoters controls viral gene expression mediated by K-Rta. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|