Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6141596 | Virology | 2010 | 11 Pages |
Abstract
We report that dengue virus (DENV) methyltransferase sequentially methylates the guanine N-7 and ribose 2â²-O positions of viral RNA cap (GpppAâm7GpppAâm7GpppAm). The order of two methylations is determined by the preference of 2â²-O methylation for substrate m7GpppA-RNA to GpppA-RNA, and the 2â²-O methylation is not absolutely dependent on the prior N-7 methylation. A mutation that completely abolished the 2â²-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 2â²-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.
Related Topics
Life Sciences
Immunology and Microbiology
Virology
Authors
Hongping Dong, David C. Chang, Xuping Xie, Ying Xiu Toh, Ka Yan Chung, Gang Zou, Julien Lescar, Siew Pheng Lim, Pei-Yong Shi,