West Nile virus encodes a microRNA-like small RNA in the 3' untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells.
West Nile virus encodes a microRNA-like small RNA in the 3' untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells.
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DOI：
10.1093/nar/gkr848
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发表时间：
2012-03
影响因子：
14.9
通讯作者：
Asgari S
中科院分区：
文献类型：
--
作者：
Hussain M;Torres S;Schnettler E;Funk A;Grundhoff A;Pijlman GP;Khromykh AA;Asgari S
西尼罗河病毒(West Nile Virus，WNV)是一组医学上重要的单链、正向RNA病毒，在世界各地引起致命的疾病暴发。黄病毒基因组的3‘非翻译区(3’-UTR)，特别是末端的3‘端茎环(3’SL)在病毒复制和病毒-宿主相互作用中具有多种功能。利用西尼罗河病毒昆津株(WNVKUN)，我们检测到一个病毒编码的小RNA，命名为Kun-miR-1，来源于3‘SL。在蚊子细胞中转录WNVKUN Pre-miRNA(3‘SL)，无论是从质粒还是从Semliki森林病毒(SFV)RNA复制子中都能产生成熟的Kun-miR-1。沉默DICER-1而不是DICER-2导致miRNA水平下降。此外，当Kun-miR-1的合成抑制剂被导入蚊子细胞时，病毒RNA的复制显著减少。利用克隆和生物信息学方法，我们确定了细胞GATA4 mRNA作为Kun-miR-1的靶标。在病毒感染过程中，蚊子细胞产生Kun-miR-1，或从质粒DNA、SFV RNA复制子或成熟的miRNA双链中产生Kun-miR-1，可增加GATA4 mRNA的积累。通过RNA沉默耗尽GATA4 mRNA导致病毒RNA复制显著减少，而Kun-miR-1 RNA模拟突变型WNVKUN病毒的增强复制，产生减少的Kun-miR-1，表明Kun-miR-1诱导GATA4在病毒复制中发挥重要作用。
West Nile virus (WNV) belongs to a group of medically important single-stranded, positive-sense RNA viruses causing deadly disease outbreaks around the world. The 3′ untranslated region (3′-UTR) of the flavivirus genome, in particular the terminal 3′ stem–loop (3′SL) fulfils multiple functions in virus replication and virus–host interactions. Using the Kunjin strain of WNV (WNVKUN), we detected a virally encoded small RNA, named KUN-miR-1, derived from 3′SL. Transcription of WNVKUN pre-miRNA (3′SL) in mosquito cells either from plasmid or Semliki Forest virus (SFV) RNA replicon resulted in the production of mature KUN-miR-1. Silencing of Dicer-1 but not Dicer-2 led to a reduction in the miRNA levels. Further, when a synthetic inhibitor of KUN-miR-1 was transfected into mosquito cells, replication of viral RNA was significantly reduced. Using cloning and bioinformatics approaches, we identified the cellular GATA4 mRNA as a target for KUN-miR-1. KUN-miR-1 produced in mosquito cells during virus infection or from plasmid DNA, SFV RNA replicon or mature miRNA duplex increased accumulation of GATA4 mRNA. Depletion of GATA4 mRNA by RNA silencing led to a significant reduction in virus RNA replication while a KUN-miR-1 RNA mimic enhanced replication of a mutant WNVKUN virus producing reduced amounts of KUN-miR-1, suggesting that GATA4-induction via KUN-miR-1 plays an important role in virus replication.
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影响因子：
16
作者：
Bogerd HP;Karnowski HW;Cai X;Shin J;Pohlers M;Cullen BR
通讯作者：
Cullen BR
影响因子：
64.8
作者：
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通讯作者：
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影响因子：
5.4
作者：
Hussain, Mazhar;Taft, Ryan J.;Asgari, Sassan
通讯作者：
Asgari, Sassan
影响因子：
4.5
作者：
Grundhoff, A;Sullivan, CS;Ganem, D
通讯作者：
Ganem, D
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.