NF-kappa(kappa)B Serves as a Cellular Sensor of KSHV Latency and Negatively Regulates K-Rta by Antagonizing the RBP-Jkappa Coactivator. Export

@article{citeulike:4137099, abstract = {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 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, 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 inhibited 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 determine 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.}, author = {Izumiya, Yoshihiro and Izumiya, Chie and Hsia, Datsun and Ellison, Thomas J J. and Luciw, Paul A A. and Kung, Hsing-Jien J.}, citeulike-article-id = {4137099}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/JVI.01999-08}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19244329}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19244329}, comment = {3.4.09}, day = {25}, doi = {10.1128/JVI.01999-08}, issn = {1098-5514}, journal = {Journal of virology}, keywords = {kshv, nfkb, rbp, rta}, month = {February}, posted-at = {2009-03-05 18:22:06}, priority = {0}, title = {NF-kappa({kappa})B Serves as a Cellular Sensor of KSHV Latency and Negatively Regulates K-Rta by Antagonizing the RBP-J{kappa} Coactivator.}, url = {http://dx.doi.org/10.1128/JVI.01999-08}, year = {2009} }

TY - JOUR ID - citeulike:4137099 L3 - citeulike-article-id:4137099 N2 - 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 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, 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 inhibited 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 determine 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. JF - Journal of virology SN - 1098-5514 TI - NF-kappa({kappa})B Serves as a Cellular Sensor of KSHV Latency and Negatively Regulates K-Rta by Antagonizing the RBP-J{kappa} Coactivator. KW - kshv KW - nfkb KW - rbp KW - rta N1 - 3.4.09 AU - Izumiya, Yoshihiro AU - Izumiya, Chie AU - Hsia, Datsun AU - Ellison, Thomas J AU - Luciw, Paul A AU - Kung, Hsing-Jien PY - 2009/02/25/ UR - http://dx.doi.org/10.1128/JVI.01999-08 ER -