Modulation of hepatitis C virus RNA accumulation and translation by DDX6 and miR-122 are mediated by separate mechanisms.

Modulation of hepatitis C virus RNA accumulation and translation by DDX6 and miR-122 are mediated by separate mechanisms.
复制标题

DOI:
10.1371/journal.pone.0067437
复制
发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Wilson JA
Wilson JA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Huys A;Thibault PA;Wilson JA

文献摘要

参考文献

被引文献

相似文献

DDX 6和其他P体蛋白是丙型肝炎病毒(HCV)通过未知机制有效复制所必需的。DDX 6与miRNA诱导的基因沉默有关,由于HCV的有效复制和翻译依赖于细胞microRNA miR-122,我们假设DDX 6在miR-122的作用机制中发挥作用。然而,通过使用多种HCV翻译和复制测定,我们发现情况并非如此。DDX 6沉默降低了HCV的复制和翻译,但不影响miR-122刺激HCV翻译或促进HCV RNA积累的能力。此外,DDX 6沉默对HCV复制和翻译的负面影响并不依赖于miR-122与HCV基因组的关联。因此,DDX 6在miR-122的活性中没有作用,并且似乎DDX 6和miR-122通过不同的途径调节HCV。在Huh7.5细胞和Hep 3B细胞中均观察到这种效应,表明这种效应不是细胞类型特异性的。由于黄病毒科中的其他病毒(包括登革热和西尼罗河病毒)的感染也会破坏P体并受DDX 6的调节,因此我们推测DDX 6可能具有支持几种黄病毒复制的共同功能。
DDX6 and other P-body proteins are required for efficient replication of Hepatitis C Virus (HCV) by unknown mechanisms. DDX6 has been implicated in miRNA induced gene silencing, and since efficient HCV replication and translation relies on the cellular microRNA, miR-122, we hypothesized that DDX6 had a role in the mechanism of action of miR-122. However, by using multiple HCV translation and replication assays we have found this is not the case. DDX6 silencing decreased HCV replication and translation, but did not affect the ability of miR-122 to stimulate HCV translation or promote HCV RNA accumulation. In addition, the negative effect of DDX6 silencing on HCV replication and translation was not dependent on miR-122 association with the HCV genome. Thus, DDX6 does not have a role in the activity of miR-122, and it appears that DDX6 and miR-122 modulate HCV through distinct pathways. This effect was seen in both Huh7.5 cells and in Hep3B cells, indicating that the effects are not cell type specific. Since infections by other viruses in the Flaviviridae family, including Dengue and West Nile Virus, also disrupt P-bodies and are regulated by DDX6, we speculate that DDX6 may have a common function that support the replication of several Flaviviruses.
DOI: 10.1126/science.1113329
发表时间: 2005-09-02
期刊: SCIENCE
影响因子: 56.9
作者:
Jopling, CL;Yi, MK;Sarnow, P
通讯作者: Sarnow, P
DOI: 10.1073/pnas.1012464108
发表时间: 2011-02-22
影响因子: 11.1
作者:
Machlin, Erica S.;Sarnow, Peter;Sagan, Selena M.
通讯作者: Sagan, Selena M.
DOI: 10.1073/pnas.0703348104
发表时间: 2007-05-22
影响因子: 11.1
作者:
Emara, Mohamed M.;Brinton, Margo A.
通讯作者: Brinton, Margo A.
mRNA 脱帽和 P 体形成的控制。
DOI: 10.1016/j.molcel.2008.11.001
发表时间: 2008-12-05
期刊: MOLECULAR CELL
影响因子: 16
作者:
Franks, Tobias M.;Lykke-Andersen, Jens
通讯作者: Lykke-Andersen, Jens
DOI: 10.1089/153685903321947996
发表时间: 2003-04-01
期刊: HYBRIDOMA AND HYBRIDOMICS
影响因子: --
作者:
Eystathioy, T;Chan, EKL;Fritzler, MJ
通讯作者: Fritzler, MJ