Activation of latent Kaposi's sarcoma-associated herpesvirus by demethylation of the promoter of the lytic transactivator Export

@article{citeulike:3067648, abstract = {Kaposi's sarcoma-associated herpesvirus (KSHV) is strongly linked to Kaposi's sarcoma, primary effusion lymphomas, and a subset of multicentric Castleman's disease. The mechanism by which this virus establishes latency and reactivation is unknown. KSHV Lyta (lytic transactivator, also named KSHV/Rta), mainly encoded by the ORF 50 gene, is a lytic switch gene for viral reactivation from latency, inasmuch as it is both essential and sufficient to drive the entire viral lytic cycle. Here we show that the Lyta promoter region was heavily methylated in latently infected cells. Treatment of primary effusion lymphoma-delivered cell lines with tetradecanoylphorbol acetate caused demethylation of the Lyta promoter and induced KSHV lytic phase in vitro. Methylation cassette assay shows demethylation of the Lyta promoter region was essential for the expression of Lyta. In vivo, biopsy samples obtained from patients with KSHV-related diseases show the most demethylation in the Lyta promoter region, whereas samples from a latently infected KSHV carrier remained in a methylated status. These results suggest a relationship among a demethylation status in the Lyta promoter, the reactivation of KSHV, and the development of KSHV-associated diseases.}, author = {Chen, Jiguo and Ueda, Keiji and Sakakibara, Shuhei and Okuno, Toshiomi and Parravicini, Carlo and Corbellino, Mario and Yamanishi, Koichi}, citeulike-article-id = {3067648}, citeulike-linkout-0 = {http://www.pnas.org/content/98/7/4119}, day = {27}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {dna, kshv, methylation}, month = {March}, number = {7}, pages = {4119--4124}, posted-at = {2008-07-31 22:25:23}, priority = {2}, title = {Activation of latent Kaposi's sarcoma-associated herpesvirus by demethylation of the promoter of the lytic transactivator}, url = {http://www.pnas.org/content/98/7/4119}, volume = {98}, year = {2001} }

TY - JOUR ID - citeulike:3067648 L3 - citeulike-article-id:3067648 N2 - Kaposi's sarcoma-associated herpesvirus (KSHV) is strongly linked to Kaposi's sarcoma, primary effusion lymphomas, and a subset of multicentric Castleman's disease. The mechanism by which this virus establishes latency and reactivation is unknown. KSHV Lyta (lytic transactivator, also named KSHV/Rta), mainly encoded by the ORF 50 gene, is a lytic switch gene for viral reactivation from latency, inasmuch as it is both essential and sufficient to drive the entire viral lytic cycle. Here we show that the Lyta promoter region was heavily methylated in latently infected cells. Treatment of primary effusion lymphoma-delivered cell lines with tetradecanoylphorbol acetate caused demethylation of the Lyta promoter and induced KSHV lytic phase in vitro. Methylation cassette assay shows demethylation of the Lyta promoter region was essential for the expression of Lyta. In vivo, biopsy samples obtained from patients with KSHV-related diseases show the most demethylation in the Lyta promoter region, whereas samples from a latently infected KSHV carrier remained in a methylated status. These results suggest a relationship among a demethylation status in the Lyta promoter, the reactivation of KSHV, and the development of KSHV-associated diseases. IS - 7 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 4124 TI - Activation of latent Kaposi's sarcoma-associated herpesvirus by demethylation of the promoter of the lytic transactivator VL - 98 SP - 4119 KW - dna KW - kshv KW - methylation AU - Chen, Jiguo AU - Ueda, Keiji AU - Sakakibara, Shuhei AU - Okuno, Toshiomi AU - Parravicini, Carlo AU - Corbellino, Mario AU - Yamanishi, Koichi PY - 2001/03/27/ UR - http://www.pnas.org/content/98/7/4119 ER -