| Literature DB >> 20655081 |
Hongping Dong1, David C Chang, Xuping Xie, Ying Xiu Toh, Ka Yan Chung, Gang Zou, Julien Lescar, Siew Pheng Lim, Pei-Yong Shi.
Abstract
We report that dengue virus (DENV) methyltransferase sequentially methylates the guanine N-7 and ribose 2'-O positions of viral RNA cap (GpppA-->m(7)GpppA-->m(7)GpppAm). The order of two methylations is determined by the preference of 2'-O methylation for substrate m(7)GpppA-RNA to GpppA-RNA, and the 2'-O methylation is not absolutely dependent on the prior N-7 methylation. A mutation that completely abolished the 2'-O methylation attenuated DENV replication in cell culture, whereas another mutation that abolished both methylations was lethal for viral replication, suggesting that N-7 methylation is more important than 2'-O methylation in viral replication. The latter mutant with lethal replication could be rescued by trans complementation using a wild-type DENV replicon. Furthermore, we found that chimeric DENVs containing the West Nile virus methyltransferase, polymerase, or full-length NS5 were nonreplicative, but the replication defect could also be rescued through trans complementation using the wild-type DENV replicon. Copyright 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID: 20655081 DOI: 10.1016/j.virol.2010.06.039
Source DB: PubMed Journal: Virology ISSN: 0042-6822 Impact factor: 3.616