miRNA对乙型肝炎病毒复制的影响及其机制研究
摘要
目的：
在我国乙型肝炎病毒(HBV)相关性肝细胞癌(hepatocellular carcinoma, HCC)发病率、死亡率均排名于疾病谱前列,严重危害人民健康,目前尚无满意的治疗方法。为此寻找新的抗HBV治疗方法成为当前急需解决的重要问题。近年发现的microRNA (miRNA),是一种广泛存在于真核生物中、大小约18-25个核苷酸(nt)的内源性单链小分子RNA,参与发育、增殖、分化、凋亡等多种生物学过程。越来越多的研究表明,miRNA也能够调控RNA和DNA病毒的复制。那么,miRNA是否也参与了HBV的复制呢?为此,我们首次研究了靶定于HBV基因组和宿主细胞基因组的人类的miRNA,为研究HBV和miRNA之间的相互作用及其机制奠定初步的实验依据,为今后抗HBV增殖药物的开发提供新的手段和分子基础。
方法：
1.分别用328种miRNA的反义链转染HepG22.2.15细胞,72小时收获上清,MTS检测细胞的增殖活性,ELISA检测表面抗原和e抗原的表达水平
2.将筛选到的对表面抗原产生有抑制作用和促进作用的miRNA的反义链梯度转染HepG22.2.15细胞,72小时收获上清,实时定量PCR检测其中HBV的拷贝数,ELISA检测表面抗原和e抗原的表达水平。
3.用miRanda, TargetScan, PicTar, miRDB和ViTa五个网站预测筛选miRNA在HBV基因组上的靶基因,对于在HBV基因组上没有靶位点的miRNA,网站预测的结果联合mRNA表达谱芯片和RT-PCR技术,对其靶基因做进一步预测。
4.分别构建筛选到的miRNA的过表达载体,包含靶位点的EGFP报告载体和靶位点突变的EGFP报告载体。并且分别在HEK293和HepG22.2.15细胞中进行荧光报告载体实验验证候选的靶基因。
结果：
1.MTS和ELISA的结果显示,在没有对细胞的增殖活性产生影响的情况下,miR-199a-3p, miR-210和miR-185抑制了HBV表面抗原的表达,而miR-370促进了病毒表面抗原的表达。
2.实时定量PCR的结果显示,miR-199a-3p, miR-210和miR-185抑制了HBV的复制,这种抑制作用具有剂量依赖性。
3.网站预测了miR-199a-3p, miR-210, miR-185和miR-370的靶基因,miR-199a-3p, miR-210分别靶定于HBV的表面抗原和表面抗原的启动子2。而在HBV上没有发现miR-185和miR-370的靶位点,通过mRNA表达谱芯片结合生物信息学的方法,我们筛选到miR-185可能的靶基因有PRKCH,ATP5B和NR1D1, miR-370可能的靶基因有FUS和TPM4。并且通过RT-PCR和芯片验证,PRKCH, ATP5B的RT-PCR结果和芯片结果相符。
4.在HEK293和HepG22.2.15两种细胞中,利用荧光报告载体实验验证了miR-199a-3p, miR-210和miR-185与候选基因的直接作用关系,结果显示,miR-199a-3p, miR-210, miR-185分别通过靶定HBsAg, HBSP2和PRKCH,从而抑制了HBV表面抗原的产生以及HBV的复制。
结论：
本研究首次发现了通过直接靶定HBV基因组或者宿主细胞基因,从而抑制病毒表面抗原产生和病毒复制的hsa-miRNA。miRNA作为病毒与宿主细胞相互作用中的调节因子(激活因子或抑制因子),在HBV的生命活动周期中具有重要作用。该研究对于阐明细胞miRNA和HBV之间错综复杂的相互作用提供了依据,对于我们理解宿主和病原体之间内在的相互调控提供很大的帮助,可能为解释病毒的组织嗜性,潜伏感染,和癌原性提供新的理论依据,而且,病毒感染相关miRNA的研究有望成为抗病毒治疗新的重要靶点。
Objective:
Chronic hepatitis B virus(HBV) infection is one of the leading cause of liver cirrhosis and hepatocellular carcinoma(HCC).Current strategies of HBV infection have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. MicroRNAs(miRNAs) are single-stranded noncoding RNAs of18to25nucleotides that play critical roles in a wide spectrum of biological processes. Accumulating evidence suggests that the miRNAs pathway also controls the replication of both RNA and DNA viruses. To address whether the miRNAs-silencing machinery influences HBV replication and antigen expression, miRNAs which can target crucial HBV genes including HBsAg or SP2genes or target cell genes including PRKCH and ATP5B genes, which play important roles in HBV infection, were studied.
Methods:
To address which miRNAs influences HBsAg expression, HBeAg expression or the proliferation of HBV producing HepG22.2.15cells, antisense oligonucleotide of special miRNAs was used to reduce the expression of endogenous miRNAs. On the basis of enzyme linked immunosorbent assay (ELISA) and CellTiter96(?) Aqueous Non-Radioactive Cell Proliferation Assay (MTS) performed on culture supernatant harvested from HepG22.2.15cells and HepG22.2.15cells72hours after transfection with miRNA ASOs, three miRNAs that inhibited HBsAg expression and one that enhanced HBsAg expression were selected.
To understand the function of these miRNAs in HBV replication, culture supernatant harvested from HepG22.2.15cells transfected with miRNA ASOs and control oligo, respectively, HBV replication was tested by quantification of Hepatitis B virus DNA.
To further analyze the mechanisms of miRNAs in controlling HBsAg expression and HBV replication, we used five well-established microRNA target prediction software-miRanda, TargetScan, PicTar, miRDB and ViTa were used to predict targets for the four miRNAs. Sequence analysis indicates that two of them do not directly target the HBV genome, which suggests that they might affect HBV replication by targeting cellular protein(s).Then, combined mRNA microarray with semi-quantitative RT-PCR was used to predict the target genes of these two miRNAs.
These prediction results were conformed by using reporter vectors with the intact putative miRNAs recognition sequence from HBV or the3'-UTR of predicted gene (pcDNA3/EGFP-UTR) or randon mutations (pcDNA3/EGFP-UTRmut) cloned downstream of the EGFP gene, respectively. HEK293and HepG22.2.15were cotransfected with pcDNA3/EGFP-UTR with or without precursor miRNAs, with or without miRNA ASOs, respectively. So did the pcDNA3/EGFP-UTRmut. GFP and RFP activity were measured with a fluorescence spectrophotometer (HITACHI F4500)48hours after transfection. Results were represented as normalized ratio of EGFP to RFP.
Results:
First, those miRNAs that influenced HBsAg expression by ELISA and MTS were screened. There are three miRNAs, miR-199a-3p, miR-210and miR-185that inhibited the expression of HBsAg and miR-370enhanced HBsAg expression.
Second, quantification of Hepatitis B virus DNA in culture supersnatant of HBV producing HepG22.2.15cells transfected with ASO indicates that miR-199a-3p, miR-210, miR-185reduce HBV production, compared with control ASO(Lacz) transfected cells.
Third, microRNA target prediction software was used to screen for potential targets of miR-199a-3p, miR-210,miR-185and miR-370. Sequence analysis indicates that miR-199a-3p and miR-210might target HBsAg and SP2, respectively. Nevertheless, sequence analysis indicates that miR-185and miR-370do not directly target the viral genome, which suggests that they might affect HBV replication by targeting cellular protein(s). So, a7,267-element human cDNA microarray was used to screen up-regulated genes owning to miR-185or miR-370being blocked down. Combining target prediction and expression profiling, three candidate miR-185-targeted genes, PRKCH, ATP5B and NR1D1and two putative target genes including FUS and TPM4for miR-370were identified.
Fourth, HBsAg, SP2and PRKCH were verified as targets for miR-199a-3p,miR-210and miR-185by EGFP reporter contructs, respectively.
Conclusion:
Up to date, this is the first report about human miRNAs that can inhibit HBV replication by targeting important HBV genes or cellular proteins. Evidence for an intricate physiological interplay between the cell's miRNAs and HBV was provided. It offers an immense opportunity not only to understand the intricacies of host-pathogen interactions, and possible explanations to viral tropism, lantency and oncogenesis, but also develop novel biomarkers and therapeutics.
在我国乙型肝炎病毒(HBV)相关性肝细胞癌(hepatocellular carcinoma, HCC)发病率、死亡率均排名于疾病谱前列,严重危害人民健康,目前尚无满意的治疗方法。为此寻找新的抗HBV治疗方法成为当前急需解决的重要问题。近年发现的microRNA (miRNA),是一种广泛存在于真核生物中、大小约18-25个核苷酸(nt)的内源性单链小分子RNA,参与发育、增殖、分化、凋亡等多种生物学过程。越来越多的研究表明,miRNA也能够调控RNA和DNA病毒的复制。那么,miRNA是否也参与了HBV的复制呢?为此,我们首次研究了靶定于HBV基因组和宿主细胞基因组的人类的miRNA,为研究HBV和miRNA之间的相互作用及其机制奠定初步的实验依据,为今后抗HBV增殖药物的开发提供新的手段和分子基础。
方法：
1.分别用328种miRNA的反义链转染HepG22.2.15细胞,72小时收获上清,MTS检测细胞的增殖活性,ELISA检测表面抗原和e抗原的表达水平
2.将筛选到的对表面抗原产生有抑制作用和促进作用的miRNA的反义链梯度转染HepG22.2.15细胞,72小时收获上清,实时定量PCR检测其中HBV的拷贝数,ELISA检测表面抗原和e抗原的表达水平。
3.用miRanda, TargetScan, PicTar, miRDB和ViTa五个网站预测筛选miRNA在HBV基因组上的靶基因,对于在HBV基因组上没有靶位点的miRNA,网站预测的结果联合mRNA表达谱芯片和RT-PCR技术,对其靶基因做进一步预测。
4.分别构建筛选到的miRNA的过表达载体,包含靶位点的EGFP报告载体和靶位点突变的EGFP报告载体。并且分别在HEK293和HepG22.2.15细胞中进行荧光报告载体实验验证候选的靶基因。
结果：
1.MTS和ELISA的结果显示,在没有对细胞的增殖活性产生影响的情况下,miR-199a-3p, miR-210和miR-185抑制了HBV表面抗原的表达,而miR-370促进了病毒表面抗原的表达。
2.实时定量PCR的结果显示,miR-199a-3p, miR-210和miR-185抑制了HBV的复制,这种抑制作用具有剂量依赖性。
3.网站预测了miR-199a-3p, miR-210, miR-185和miR-370的靶基因,miR-199a-3p, miR-210分别靶定于HBV的表面抗原和表面抗原的启动子2。而在HBV上没有发现miR-185和miR-370的靶位点,通过mRNA表达谱芯片结合生物信息学的方法,我们筛选到miR-185可能的靶基因有PRKCH,ATP5B和NR1D1, miR-370可能的靶基因有FUS和TPM4。并且通过RT-PCR和芯片验证,PRKCH, ATP5B的RT-PCR结果和芯片结果相符。
4.在HEK293和HepG22.2.15两种细胞中,利用荧光报告载体实验验证了miR-199a-3p, miR-210和miR-185与候选基因的直接作用关系,结果显示,miR-199a-3p, miR-210, miR-185分别通过靶定HBsAg, HBSP2和PRKCH,从而抑制了HBV表面抗原的产生以及HBV的复制。
结论：
本研究首次发现了通过直接靶定HBV基因组或者宿主细胞基因,从而抑制病毒表面抗原产生和病毒复制的hsa-miRNA。miRNA作为病毒与宿主细胞相互作用中的调节因子(激活因子或抑制因子),在HBV的生命活动周期中具有重要作用。该研究对于阐明细胞miRNA和HBV之间错综复杂的相互作用提供了依据,对于我们理解宿主和病原体之间内在的相互调控提供很大的帮助,可能为解释病毒的组织嗜性,潜伏感染,和癌原性提供新的理论依据,而且,病毒感染相关miRNA的研究有望成为抗病毒治疗新的重要靶点。
Objective:
Chronic hepatitis B virus(HBV) infection is one of the leading cause of liver cirrhosis and hepatocellular carcinoma(HCC).Current strategies of HBV infection have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. MicroRNAs(miRNAs) are single-stranded noncoding RNAs of18to25nucleotides that play critical roles in a wide spectrum of biological processes. Accumulating evidence suggests that the miRNAs pathway also controls the replication of both RNA and DNA viruses. To address whether the miRNAs-silencing machinery influences HBV replication and antigen expression, miRNAs which can target crucial HBV genes including HBsAg or SP2genes or target cell genes including PRKCH and ATP5B genes, which play important roles in HBV infection, were studied.
Methods:
To address which miRNAs influences HBsAg expression, HBeAg expression or the proliferation of HBV producing HepG22.2.15cells, antisense oligonucleotide of special miRNAs was used to reduce the expression of endogenous miRNAs. On the basis of enzyme linked immunosorbent assay (ELISA) and CellTiter96(?) Aqueous Non-Radioactive Cell Proliferation Assay (MTS) performed on culture supernatant harvested from HepG22.2.15cells and HepG22.2.15cells72hours after transfection with miRNA ASOs, three miRNAs that inhibited HBsAg expression and one that enhanced HBsAg expression were selected.
To understand the function of these miRNAs in HBV replication, culture supernatant harvested from HepG22.2.15cells transfected with miRNA ASOs and control oligo, respectively, HBV replication was tested by quantification of Hepatitis B virus DNA.
To further analyze the mechanisms of miRNAs in controlling HBsAg expression and HBV replication, we used five well-established microRNA target prediction software-miRanda, TargetScan, PicTar, miRDB and ViTa were used to predict targets for the four miRNAs. Sequence analysis indicates that two of them do not directly target the HBV genome, which suggests that they might affect HBV replication by targeting cellular protein(s).Then, combined mRNA microarray with semi-quantitative RT-PCR was used to predict the target genes of these two miRNAs.
These prediction results were conformed by using reporter vectors with the intact putative miRNAs recognition sequence from HBV or the3'-UTR of predicted gene (pcDNA3/EGFP-UTR) or randon mutations (pcDNA3/EGFP-UTRmut) cloned downstream of the EGFP gene, respectively. HEK293and HepG22.2.15were cotransfected with pcDNA3/EGFP-UTR with or without precursor miRNAs, with or without miRNA ASOs, respectively. So did the pcDNA3/EGFP-UTRmut. GFP and RFP activity were measured with a fluorescence spectrophotometer (HITACHI F4500)48hours after transfection. Results were represented as normalized ratio of EGFP to RFP.
Results:
First, those miRNAs that influenced HBsAg expression by ELISA and MTS were screened. There are three miRNAs, miR-199a-3p, miR-210and miR-185that inhibited the expression of HBsAg and miR-370enhanced HBsAg expression.
Second, quantification of Hepatitis B virus DNA in culture supersnatant of HBV producing HepG22.2.15cells transfected with ASO indicates that miR-199a-3p, miR-210, miR-185reduce HBV production, compared with control ASO(Lacz) transfected cells.
Third, microRNA target prediction software was used to screen for potential targets of miR-199a-3p, miR-210,miR-185and miR-370. Sequence analysis indicates that miR-199a-3p and miR-210might target HBsAg and SP2, respectively. Nevertheless, sequence analysis indicates that miR-185and miR-370do not directly target the viral genome, which suggests that they might affect HBV replication by targeting cellular protein(s). So, a7,267-element human cDNA microarray was used to screen up-regulated genes owning to miR-185or miR-370being blocked down. Combining target prediction and expression profiling, three candidate miR-185-targeted genes, PRKCH, ATP5B and NR1D1and two putative target genes including FUS and TPM4for miR-370were identified.
Fourth, HBsAg, SP2and PRKCH were verified as targets for miR-199a-3p,miR-210and miR-185by EGFP reporter contructs, respectively.
Conclusion:
Up to date, this is the first report about human miRNAs that can inhibit HBV replication by targeting important HBV genes or cellular proteins. Evidence for an intricate physiological interplay between the cell's miRNAs and HBV was provided. It offers an immense opportunity not only to understand the intricacies of host-pathogen interactions, and possible explanations to viral tropism, lantency and oncogenesis, but also develop novel biomarkers and therapeutics.
引文
1.Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD. A distinct small RNA pathway silences selfish genetic elements in the germline. Science (New York, NY. 2006 Jul 21;313(5785):320-4.
2.Hamilton A, Voinnet O, Chappell L, Baulcombe D. Two classes of short interfering RNA in RNA silencing. The EMBO journal.2002 Sep 2;21(17):4671-9.
3.Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell.1993 Dec 3;75(5):843-54.
4.Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell.2005 Jan 14;120(1):21-4.
5.Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, et al. Systematic discovery of regulatory motifs in human promoters and 3'UTRs by comparison of several mammals. Nature.2005 Mar 17;434(7031):338-45.
6. Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, et al. A uniform system for microRNA annotation. RNA (New York, NY.2003 Mar;9(3):277-9.
7.Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell.2004 Jan23;116(2):281-97.
8.Cullen BR. Transcription and processing of human microRNA precursors. Molecular cell.2004 Dec 22;16(6):861-5.
9.Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, et al. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 2005 Dec 1;438(7068):671-4.
10. Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science (New York, NY.2004 Apr 23;304(5670):594-6.
11. Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proceedings of the National Academy of Sciences of the United States of America. 2006 Mar 14; 103(11):4034-9.
12.Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer research.2005 Jul 15;65(14):6029-33.
13.Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science (New York, NY.2004 Apr 30;304(5671):734-6.
14.Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, et al. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS pathogens.2006 Mar;2(3):e23.
15.Jin WB, Wu FL, Kong D, Guo AG. HBV-encoded microRNA candidate and its target. Computational biology and chemistry.2007 Apr;31(2):124-6.
16.Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, et al. A cellular microRNA mediates antiviral defense in human cells. Science (New York, NY. 2005 Apr 22;308(5721):557-60.
17.Sullivan CS, Ganem D. MicroRNAs and viral infection. Molecular cell.2005 Oct 7;20(1):3-7.
18.Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science (New York, NY. 2005 Sep 2;309(5740):1577-81.
19.Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell metabolism.2006 Feb;3(2):87-98.
20.Bennasser Y, Yeung ML, Jeang KT. HIV-1 TAR RNA subverts RNA interference in transfected cells through sequestration of TAR RNA-binding protein, TRBP. The Journal of biological chemistry.2006 Sep 22;281(38):27674-8.
21.Bennasser Y LS, Benkirane M. Evidence that HIV-1 Encodes an siRNA and a Suppressor of RNA Silencing. Immunity 2005; 22(5):607-19.
22.Dunoyer P, Lecellier CH, Parizotto EA, Himber C, Voinnet O. Probing the microRNA and small interfering RNA pathways with virus-encoded suppressors of RNA silencing. The Plant cell.2004 May; 16(5):1235-50.
23.Lakatos L, Szittya G, Silhavy D, Burgyan J. Molecular mechanism of RNA silencing suppression mediated by p19 protein of tombusviruses. The EMBO journal. 2004 Feb 25;23(4):876-84.
24.Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature.2005 Jun2;435(7042):682-6.
25.Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature. 2006 Jul 6;442(7098):82-5.
26.Omoto S, Ito M, Tsutsumi Y, Ichikawa Y, Okuyama H, Brisibe EA, et al. HIV-1 nef suppression by virally encoded microRNA. Retrovirology.2004; 1:44.
27.Giladi H, Ketzinel-Gilad M, Rivkin L, Felig Y, Nussbaum O, Galun E. Small interfering RNA inhibits hepatitis B virus replication in mice. Mol Ther.2003 Nov;8(5):769-76.
28.Tang KF, Xie J, Chen M, Liu Q, Zhou XY, Zeng W, et al. Knockdown of damage-specific DNA binding protein 1 (DDB1) enhances the HBx-siRNA-mediated inhibition of HBV replication. Biologicals.2008 May;36(3):177-83.
29.Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science (New York, NY.2004 Apr 30;304(5671):734-6.
30.Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, et al. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS pathogens.2006 Mar;2(3):e23.
31.Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature.2005 Jun 2;435(7042):682-6.
32.Barth S, Pfuhl T, Mamiani A, Ehses C, Roemer K, Kremmer E, et al. Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5. Nucleic acids research.2008 Feb;36(2):666-75.
33.Samols MA, Hu J, Skalsky RL, Renne R. Cloning and identification of a microRNA cluster within the latency-associated region of Kaposi's sarcoma-associated herpesvirus. Journal of virology.2005 Jul;79(14):9301-5.
34.Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proceedings of the National Academy of Sciences of the United States of America.2005 Apr 12;102(15):5570-5.
35.Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature. 2006 Jul 6;442(7098):82-5.
36.Omoto S, Fujii YR. Regulation of human immunodeficiency virus 1 transcription by nef microRNA. The Journal of general virology.2005 Mar;86(Pt 3):751-5.
37.Bennasser Y, Le SY, Yeung ML, Jeang KT. HIV-1 encoded candidate micro-RNAs and their cellular targets. Retrovirology.2004; 1:43.
38.Couturier JP, Root-Bernstein RS. HIV may produce inhibitory microRNAs (miRNAs) that block production of CD28, CD4 and some interleukins. Journal of theoretical biology.2005 Jul 21;235(2):169-84.
39.Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell. 2004 Jan 23;116(2):281-97.
40.Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, et al. The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science (New York, NY.2005 Dec 16;310(5755):1817-21.
41.Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3' UTR evolution. Cell.2005 Dec 16; 123(6):1133-46.
42.Gitlin L, Andino R. Nucleic acid-based immune system:the antiviral potential of mammalian RNA silencing. Journal of virology.2003 Jul;77(13):7159-65.
43.Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, et al. A cellular microRNA mediates antiviral defense in human cells. Science (New York, NY. 2005 Apr 22;308(5721):557-60.
44.Linial ML. Foamy viruses are unconventional retroviruses. Journal of virology. 1999 Mar;73(3):1747-55.
45.Robinson Triboulet BM, Yea-Lin,Christine Chable-Bessia,. Suppression of miRNA-silencing pathway by HIV-1 during virus replication. Science. 2007;315(16):1579-82.
46.Hariharan M, Scaria V, Pillai B, Brahmachari SK. Targets for human encoded microRNAs in HIV genes. Biochemical and biophysical research communications. 2005 Dec 2;337(4):1214-8.
47.Yeung ML, Bennasser Y, Myers TG, Jiang G, Benkirane M, Jeang KT. Changes in microRNA expression profiles in HIV-1-transfected human cells. Retrovirology. 2005;2:81.
48.Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, et al. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nature medicine. 2007 Oct;13(10):1241-7.
49.Scaria V, Hariharan M, Maiti S, Pillai B, Brahmachari SK. Host-virus interaction: a new role for microRNAs. Retrovirology.2006;3:68.
50.Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science (New York, NY. 2005 Sep 2;309(5740):1577-81.
51.Ikeda M, Yi M, Li K, Lemon SM. Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells. Journal of virology.2002 Mar;76(6):2997-3006.
52.Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene.2006 Apr 20;25(17):2537-45.
53.Jin WB, Wu FL, Kong D, Guo AG. HBV-encoded microRNA candidate and its target. Computational biology and chemistry.2007 Apr;31(2):124-6.
54.Lai EC, Tomancak P, Williams RW, Rubin GM. Computational identification of Drosophila microRNA genes. Genome biology.2003;4(7):R42.
55.Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic acids research.2006 Jan 1;34(Database issue):D 140-4.
56.Doran J, Strauss WM. Bio-informatic trends for the determination of miRNA-target interactions in mammals. DNA and cell biology.2007 May;26(5):353-60.
57.Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell.2003 Dec 26; 115(7):787-98.
58.John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. PLoS biology.2004 Nov;2(11):e363.
59.Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nature genetics.2005 May;37(5):495-500.
60.Chiromatzo AO, Oliveira TY, Pereira G, Costa AY, Montesco CA, Gras DE, et al. miRNApath:a database of miRNAs, target genes and metabolic pathways. Genet Mol Res.2007;6(4):859-65.
61.Hsu SD, Chu CH, Tsou AP, Chen SJ, Chen HC, Hsu PW, et al. miRNAMap 2.0: genomic maps of microRNAs in metazoan genomes. Nucleic acids research.2008 Jan;36(Database issue):D 165-9.
62.Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature.2004 Nov 11;432(7014):226-30.
63.Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell.2005 Dec 2;123(5):819-31.
64.Jansen PL. [Improved survival and less hepatocellar carcinoma following the successful treatment of chornic hepatitis B]. Nederlands tijdschrift voor geneeskunde. 2005 Jul 2;149(27):1495-7.
65.Peng J, Zhao Y, Mai J, Pang WK, Wei X, Zhang P, et al. Inhibition of hepatitis B virus replication by various RNAi constructs and their pharmacodynamic properties. The Journal of general virology.2005 Dec;86(Pt 12):3227-34.
66.McManus MT, Sharp PA. Gene silencing in mammals by small interfering RNAs. Nature reviews.2002 Oct;3(10):737-47.
67.Lupberger J, Brino L, Baumert TF. RNAi:a powerful tool to unravel hepatitis C virus-host interactions within the infectious life cycle. Journal of hepatology.2008 Mar;48(3):523-5.
68.Maissel A MM, Shtutman M, Shahaf G, Livneh E. PKCeta is localized in the Golgi, ER and nuclear envelope and translocates to the nuclear envelope upon PMA activation and serum-starvation:Clb domain and the pseudosubstrate containing fragment target PKCeta to the Golgi and the nuclear envelope. Cell Signal. 2006; 18(8):1127-39.
69.Osada S, Mizuno K, Saido TC, Akita Y, Suzuki K, Kuroki T, et al. A phorbol ester receptor/protein kinase, nPKC eta, a new member of the protein kinase C family predominantly expressed in lung and skin. The Journal of biological chemistry.1990 Dec 25;265(36):22434-40.
70.Greif H, Ben-Chaim J, Shimon T, Bechor E, Eldar H, Livneh E. The protein kinase C-related PKC-L(eta) gene product is localized in the cell nucleus. Molecular and cellular biology.1992 Mar; 12(3):1304-11.
71.Uht RM AS, Martin PM, Riggan AE, Hussaini IM. The protein kinase C-eta isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway. Oncogene.2007 26(20):2885-93.
72.Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, et al. A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nature genetics.2007 Feb;39(2):212-7.
73.Takata Y, Hamada D, Miyatake K, Nakano S, Shinomiya F, Scafe CR, et al. Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme and rheumatoid arthritis in the Japanese population. Arthritis and rheumatism.2007 Jan;56(1):30-42.
74.Aeder SE MP, Soh JW, Hussaini IM. PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene.2004 Dec 2;;23(56):9062-9.
75.Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell.2000 Oct 13;103(2):239-52.
76.Shaulian E, Karin M. AP-1 in cell proliferation and survival. Oncogene.2001 Apr 30;20(19):2390-400.
77.Andrisani OM, Barnabas S. The transcriptional function of the hepatitis B virus X protein and its role in hepatocarcinogenesis (Review). International journal of oncology.1999 Aug;15(2):373-9.
78.Arbuthnot P, Capovilla A, Kew M. Putative role of hepatitis B virus X protein in hepatocarcinogenesis:effects on apoptosis, DNA repair, mitogen-activated protein kinase and JAK/STAT pathways. Journal of gastroenterology and hepatology.2000 Apr;15(4):357-68.
79.Maguire HF, Hoeffler JP, Siddiqui A. HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions. Science (New York, NY.1991 May 10;252(5007):842-4.
60.Benn J, Schneider RJ. Hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade. Proceedings of the National Academy of Sciences of the United States of America.1994 Oct 25;91(22):10350-4.
81.HJ. LYKSK. Phosphorylation of purified recombinant hepatitis B virus·X protein by mitogen activated protein kinase and Protein kinase C in vitro..J virol Methods.2001;95(1-2):1-10.
82.Binetruy B, Smeal T, Karin M. Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. Nature.1991 May 9;351(6322):122-7.
83.R HFK. Hepatitis B virus tranac fiptional ac tivators:mechanisms and possible role in oncngenesis.. J Viral Hepat.1996;3(3):109-21.
84.Ye L, Qi J, Li G, Tao D, Song S. The effect of HBx gene on the apoptosis of hepatic cells. Journal of Huazhong University of Science and Technology Medical sciences= Hua zhong ke ji da xue xue bao Yi xue Ying De wen ban= Huazhong keji daxue xuebao.2007 Apr;27(2):167-9.
85.Zhou MX, Watabe M, Watabe K. The X-gene of human hepatitis B virus transactivates the c-jun and alpha-fetoprotein genes. Archives of virology. 1994;134(3-4):369-78.
1. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell. 2004 Jan 23; 116(2):281-97.
2. Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell.2005 Dec 16;123(6):1133-46.
3. Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, et al. The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science (New York, NY.2005 Dec 16;310(5755):1817-21.
4. Cullen BR. Transcription and processing of human microRNA precursors. Molecular cell.2004 Dec 22;16(6):861-5.
5. Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA (New York, NY. 2004 Dec;10(12):1957-66.
6. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase Ⅱ. The EMBO journal.2004 Oct 13;23(20):4051-60.
7. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature.2004 Nov 11;432(7014):231-5.
8. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature.2004 Nov 11;432(7014):235-40.
9. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & development.2003 Dec 15;17(24):3011-6.
10. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science (New York, NY.2004 Jan 2;303(5654):95-8.
11. Zeng Y, Cullen BR. Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic acids research.2004;32(16):4776-85.
12. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature.2005 Aug 4;436(7051):740-4.
13. Maniataki E, Mourelatos Z. A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Genes & development.2005 Dec 15;19(24):2979-90.
14. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science (New York, NY. 2004 Sep 3;305(5689):1437-41.
15. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNA and siRNAs. Molecular cell. 2004 Jul 23; 15(2):185-97.
16. Schwarz DS, Hutvagner G, Haley B, Zamore PD. Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. Molecular cell. 2002 Sep;10(3):537-48.
17. Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science (New York, NY.2002 Sep 20;297(5589):2056-60.
18. Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proceedings of the National Academy of Sciences of the United States of America.2003 Aug 19;100(17):9779-84.
19. Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science (New York, NY.2004 Apr 23;304(5670):594-6.
20. Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental biology.1999 Dec 15;216(2):671-80.
21. Zeng Y, Wagner EJ, Cullen BR. Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Molecular cell.2002 Jun;9(6):1327-33.
22. Doench JG, Petersen CP, Sharp PA. siRNAs can function as miRNA. Genes & development.2003 Feb 15;17(4):438-42.
23. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature.2003 Sep 25;425(6956):415-9.
24. Zeng Y, Cullen BR. Sequence requirements for micro RNA processing and function in human cells. RNA (New York, NY.2003 Jan;9(1):112-23.
25. Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, et al. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS pathogens.2006 Mar;2(3):e23.
26. Grundhoff A, Sullivan CS, Ganem D. A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. RNA (New York, NY.2006 May;12(5):733-50.
27. Grey F, Antoniewicz A, Allen E, Saugstad J, McShea A, Carrington JC, et al. Identification and characterization of human cytomegalovirus-encoded microRNAs. Journal of virology.2005 Sep;79(18):12095-9.
28. Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grasser FA, et al. Identification of microRNAs of the herpesvirus family. Nature methods.2005 Apr;2(4):269-76.
29. Fraser NW, Block TM, Spivack JG. The latency-associated transcripts of herpes simplex virus:RNA in search of function. Virology.1992 Nov; 191(1):1-8.
30. Branco FJ, Fraser NW. Herpes simplex virus type 1 latency-associated transcript expression protects trigeminal ganglion neurons from apoptosis. Journal of virology. 2005 Jul;79(14):9019-25.
31. Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science (New York, NY.2004 Apr 30;304(5671):734-6.
32. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proceedings of the National Academy of Sciences of the United States of America; 2005. p.5570-5.
33. Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature.2005 Jun 2;435(7042):682-6.
34. Mathews MB, Shenk T. Adenovirus virus-associated RNA and translation control. Journal of virology.1991 Nov;65(11):5657-62.
35. Thimmappaya B, Weinberger, C, Schneider, R.J. & Shenk,. Adenovirus VA1 RNA is required for efficient translation of viral mRNAs at late times after infection. Cell.1982;31,:543-51.
36. Gwizdek Cea. Terminal minihelix, a novel RNA motif that directs polymerase III transcripts to the cell cytoplasm. J Biol Chem 2001;276:25910-8.
37. Cuddihy AR, et al.. The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro.. Oncogene.1999; 18:2690-702.
38. Williams BR. PKR; a sentinel kinase for cellular stress. Oncogene.1999(18): 6112-20.
39. Zhang F, et al. Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop.. J Biol Chem.2001;276:24946-58.
40. Sano M, Kato Y, Taira K. Sequence-specific interference by small RNAs derived from adenovirus VAI RNA. FEBS letters.2006 Mar 6;580(6):1553-64.
41. Bennasser Y, Le SY, Yeung ML, Jeang KT. HIV-1 encoded candidate micro-RNAs and their cellular targets. Retrovirology.2004; 1:43.
42. Ouellet DL, I. Plante, et al. IO. "." Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. Nucleic Acids Res. 2008.
43. Omoto S, Ito M, Tsutsumi Y, Ichikawa Y, Okuyama H, Brisibe EA, et al. HIV-1 nef suppression by virally encoded microRNA. Retrovirology.2004; 1:44.
44. Cai X, Cullen BR. Transcriptional origin of Kaposi's sarcoma-associated herpesvirus microRNAs. Journal of virology.2006 Mar;80(5):2234-42.
45. Andersson MGea. Suppression of RNA interference by adenovirus virus-associated RNA. J Virol 2005;79:9556-65
46. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proceedings of the National Academy of Sciences of the United States of America.2005 Apr 12;102(15):5570-5.
47. Samols MA, Hu J, Skalsky RL, Renne R. Cloning and identification of a microRNA cluster within the latency-associated region of Kaposi's sarcoma-associated herpesvirus. Journal of virology.2005 Jul;79(14):9301-5.
48. Barth S, Pfuhl T, Mamiani A, Ehses C, Roemer K, Kremmer E, et al. Epstein-Barr virus-encoded micro RNA miR-BART2 down-regulates the viral DNA polymerase BALF5. Nucleic acids research.2008 Feb;36(2):666-75.
49. Tortorella D, Gewurz, B.E., Furman, M.H., Schust, D.J. & Ploegh, H.L. Viral subversion of the immune system. Annu Rev Immunol 2000(18):861-926
50. Katze MG, He Y, Gale M, Jr. Viruses and interferon:a fight for supremacy. Nature reviews.2002 Sep;2(9):675-87.
51. Macrae AI, Dutia BM, Milligan S, Brownstein DG, Allen DJ, Mistrikova J, et al. Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis. Journal of virology.2001 Jun;75(11):5315-27.
52. Omoto S, Fujii YR. Regulation of human immunodeficiency virus 1 transcription by nef micro RN A. The Journal of general virology.2005 Mar;86(Pt 3):751-5.
53. Samols MA, Skalsky RL, Maldonado AM, Riva A, Lopez MC, Baker HV, et al. Identification of cellular genes targeted by KSHV-encoded microRNAs. PLoS pathogens.2007 May 11;3(5):e65.
54. Murphy E, Vanicek J, Robins H, Shenk T, Levine AJ. Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency. Proceedings of the National Academy of Sciences of the United States of America.2008 Apr 8;105(14):5453-8.
55. Couturier JP, Root-Bernstein RS. HIV may produce inhibitory microRNAs (miRNA) that block production of CD28, CD4 and some interleukins. Journal of theoretical biology.2005 Jul 21;235(2):169-84.
56. Cui C, Griffiths A, Li G, Silva LM, Kramer MF, Gaasterland T, et al. Prediction and identification of herpes simplex virus 1-encoded microRNAs. Journal of virology. 2006Jun;80(11):5499-508.
57. Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature.2006 Jul 6;442(7098):82-5.
58. Kim do N, Chae HS, Oh ST, Kang JH, Park CH, Park WS, et al. Expression of viral microRNAs in Epstein-Barr virus-associated gastric carcinoma. Journal of virology.2007 Jan;81(2):1033-6.
59. Stern-Ginossar N, Elefant N, Zimmermann A, Wolf DG, Saleh N, Biton M, et al. Host immune system gene targeting by a viral miRNA. Science (New York, NY. 2007 Jul 20;317(5836):376-81.
60. Gitlin L, Andino R. Nucleic acid-based immune system:the antiviral potential of mammalian RNA silencing. Journal of virology.2003 Jul;77(13):7159-65.
61. Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, et al. A cellular microRNA mediates antiviral defense in human cells. Science (New York, NY.2005 Apr 22;308(5721):557-60.
62. Linial ML. Foamy viruses are unconventional retroviruses. Journal of virology. 1999 Mar;73(3):1747-55.
63. Robinson Triboulet BM, Yea-Lin,Christine Chable-Bessia,. Suppression of miRNA-silencing pathway by HIV-1 during virus replication. Science. 2007;315(16):1579-82.
64. Hariharan M, Scaria V, Pillai B, Brahmachari SK. Targets for human encoded microRNAs in HIV genes. Biochemical and biophysical research communications. 2005 Dec 2;337(4):1214-8.
65. Yeung ML, Bennasser Y, Myers TG, Jiang G, Benkirane M, Jeang KT. Changes in microRNA expression profiles in HIV-1-transfected human cells. Retrovirology. 2005;2:81.
66. Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, et al. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+T lymphocytes. Nature medicine.2007 Oct;13(10):1241-7.
67. Scaria V, Hariharan M, Maiti S, Pillai B, Brahmachari SK. Host-virus interaction: a new role for microRNAs. Retrovirology.2006;3:68.
68. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science (New York, NY. 2005 Sep 2;309(5740):1577-81.
69. Ikeda M, Yi M, Li K, Lemon SM. Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells. Journal of virology.2002 Mar;76(6):2997-3006.
70. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell metabolism.2006 Feb;3(2):87-98.
71. Kapadia SB, and F. V. Chisari. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids.. Proc Natl AcadSci 2005(102):2561-6.
72. Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene.2006 Apr 20;25(17):2537-45.
2.Hamilton A, Voinnet O, Chappell L, Baulcombe D. Two classes of short interfering RNA in RNA silencing. The EMBO journal.2002 Sep 2;21(17):4671-9.
3.Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell.1993 Dec 3;75(5):843-54.
4.Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell.2005 Jan 14;120(1):21-4.
5.Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, et al. Systematic discovery of regulatory motifs in human promoters and 3'UTRs by comparison of several mammals. Nature.2005 Mar 17;434(7031):338-45.
6. Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen X, et al. A uniform system for microRNA annotation. RNA (New York, NY.2003 Mar;9(3):277-9.
7.Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell.2004 Jan23;116(2):281-97.
8.Cullen BR. Transcription and processing of human microRNA precursors. Molecular cell.2004 Dec 22;16(6):861-5.
9.Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, et al. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 2005 Dec 1;438(7068):671-4.
10. Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science (New York, NY.2004 Apr 23;304(5670):594-6.
11. Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proceedings of the National Academy of Sciences of the United States of America. 2006 Mar 14; 103(11):4034-9.
12.Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer research.2005 Jul 15;65(14):6029-33.
13.Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science (New York, NY.2004 Apr 30;304(5671):734-6.
14.Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, et al. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS pathogens.2006 Mar;2(3):e23.
15.Jin WB, Wu FL, Kong D, Guo AG. HBV-encoded microRNA candidate and its target. Computational biology and chemistry.2007 Apr;31(2):124-6.
16.Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, et al. A cellular microRNA mediates antiviral defense in human cells. Science (New York, NY. 2005 Apr 22;308(5721):557-60.
17.Sullivan CS, Ganem D. MicroRNAs and viral infection. Molecular cell.2005 Oct 7;20(1):3-7.
18.Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science (New York, NY. 2005 Sep 2;309(5740):1577-81.
19.Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell metabolism.2006 Feb;3(2):87-98.
20.Bennasser Y, Yeung ML, Jeang KT. HIV-1 TAR RNA subverts RNA interference in transfected cells through sequestration of TAR RNA-binding protein, TRBP. The Journal of biological chemistry.2006 Sep 22;281(38):27674-8.
21.Bennasser Y LS, Benkirane M. Evidence that HIV-1 Encodes an siRNA and a Suppressor of RNA Silencing. Immunity 2005; 22(5):607-19.
22.Dunoyer P, Lecellier CH, Parizotto EA, Himber C, Voinnet O. Probing the microRNA and small interfering RNA pathways with virus-encoded suppressors of RNA silencing. The Plant cell.2004 May; 16(5):1235-50.
23.Lakatos L, Szittya G, Silhavy D, Burgyan J. Molecular mechanism of RNA silencing suppression mediated by p19 protein of tombusviruses. The EMBO journal. 2004 Feb 25;23(4):876-84.
24.Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature.2005 Jun2;435(7042):682-6.
25.Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature. 2006 Jul 6;442(7098):82-5.
26.Omoto S, Ito M, Tsutsumi Y, Ichikawa Y, Okuyama H, Brisibe EA, et al. HIV-1 nef suppression by virally encoded microRNA. Retrovirology.2004; 1:44.
27.Giladi H, Ketzinel-Gilad M, Rivkin L, Felig Y, Nussbaum O, Galun E. Small interfering RNA inhibits hepatitis B virus replication in mice. Mol Ther.2003 Nov;8(5):769-76.
28.Tang KF, Xie J, Chen M, Liu Q, Zhou XY, Zeng W, et al. Knockdown of damage-specific DNA binding protein 1 (DDB1) enhances the HBx-siRNA-mediated inhibition of HBV replication. Biologicals.2008 May;36(3):177-83.
29.Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science (New York, NY.2004 Apr 30;304(5671):734-6.
30.Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, et al. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS pathogens.2006 Mar;2(3):e23.
31.Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature.2005 Jun 2;435(7042):682-6.
32.Barth S, Pfuhl T, Mamiani A, Ehses C, Roemer K, Kremmer E, et al. Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5. Nucleic acids research.2008 Feb;36(2):666-75.
33.Samols MA, Hu J, Skalsky RL, Renne R. Cloning and identification of a microRNA cluster within the latency-associated region of Kaposi's sarcoma-associated herpesvirus. Journal of virology.2005 Jul;79(14):9301-5.
34.Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proceedings of the National Academy of Sciences of the United States of America.2005 Apr 12;102(15):5570-5.
35.Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature. 2006 Jul 6;442(7098):82-5.
36.Omoto S, Fujii YR. Regulation of human immunodeficiency virus 1 transcription by nef microRNA. The Journal of general virology.2005 Mar;86(Pt 3):751-5.
37.Bennasser Y, Le SY, Yeung ML, Jeang KT. HIV-1 encoded candidate micro-RNAs and their cellular targets. Retrovirology.2004; 1:43.
38.Couturier JP, Root-Bernstein RS. HIV may produce inhibitory microRNAs (miRNAs) that block production of CD28, CD4 and some interleukins. Journal of theoretical biology.2005 Jul 21;235(2):169-84.
39.Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell. 2004 Jan 23;116(2):281-97.
40.Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, et al. The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science (New York, NY.2005 Dec 16;310(5755):1817-21.
41.Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3' UTR evolution. Cell.2005 Dec 16; 123(6):1133-46.
42.Gitlin L, Andino R. Nucleic acid-based immune system:the antiviral potential of mammalian RNA silencing. Journal of virology.2003 Jul;77(13):7159-65.
43.Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, et al. A cellular microRNA mediates antiviral defense in human cells. Science (New York, NY. 2005 Apr 22;308(5721):557-60.
44.Linial ML. Foamy viruses are unconventional retroviruses. Journal of virology. 1999 Mar;73(3):1747-55.
45.Robinson Triboulet BM, Yea-Lin,Christine Chable-Bessia,. Suppression of miRNA-silencing pathway by HIV-1 during virus replication. Science. 2007;315(16):1579-82.
46.Hariharan M, Scaria V, Pillai B, Brahmachari SK. Targets for human encoded microRNAs in HIV genes. Biochemical and biophysical research communications. 2005 Dec 2;337(4):1214-8.
47.Yeung ML, Bennasser Y, Myers TG, Jiang G, Benkirane M, Jeang KT. Changes in microRNA expression profiles in HIV-1-transfected human cells. Retrovirology. 2005;2:81.
48.Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, et al. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nature medicine. 2007 Oct;13(10):1241-7.
49.Scaria V, Hariharan M, Maiti S, Pillai B, Brahmachari SK. Host-virus interaction: a new role for microRNAs. Retrovirology.2006;3:68.
50.Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science (New York, NY. 2005 Sep 2;309(5740):1577-81.
51.Ikeda M, Yi M, Li K, Lemon SM. Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells. Journal of virology.2002 Mar;76(6):2997-3006.
52.Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene.2006 Apr 20;25(17):2537-45.
53.Jin WB, Wu FL, Kong D, Guo AG. HBV-encoded microRNA candidate and its target. Computational biology and chemistry.2007 Apr;31(2):124-6.
54.Lai EC, Tomancak P, Williams RW, Rubin GM. Computational identification of Drosophila microRNA genes. Genome biology.2003;4(7):R42.
55.Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic acids research.2006 Jan 1;34(Database issue):D 140-4.
56.Doran J, Strauss WM. Bio-informatic trends for the determination of miRNA-target interactions in mammals. DNA and cell biology.2007 May;26(5):353-60.
57.Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell.2003 Dec 26; 115(7):787-98.
58.John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human MicroRNA targets. PLoS biology.2004 Nov;2(11):e363.
59.Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nature genetics.2005 May;37(5):495-500.
60.Chiromatzo AO, Oliveira TY, Pereira G, Costa AY, Montesco CA, Gras DE, et al. miRNApath:a database of miRNAs, target genes and metabolic pathways. Genet Mol Res.2007;6(4):859-65.
61.Hsu SD, Chu CH, Tsou AP, Chen SJ, Chen HC, Hsu PW, et al. miRNAMap 2.0: genomic maps of microRNAs in metazoan genomes. Nucleic acids research.2008 Jan;36(Database issue):D 165-9.
62.Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature.2004 Nov 11;432(7014):226-30.
63.Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell.2005 Dec 2;123(5):819-31.
64.Jansen PL. [Improved survival and less hepatocellar carcinoma following the successful treatment of chornic hepatitis B]. Nederlands tijdschrift voor geneeskunde. 2005 Jul 2;149(27):1495-7.
65.Peng J, Zhao Y, Mai J, Pang WK, Wei X, Zhang P, et al. Inhibition of hepatitis B virus replication by various RNAi constructs and their pharmacodynamic properties. The Journal of general virology.2005 Dec;86(Pt 12):3227-34.
66.McManus MT, Sharp PA. Gene silencing in mammals by small interfering RNAs. Nature reviews.2002 Oct;3(10):737-47.
67.Lupberger J, Brino L, Baumert TF. RNAi:a powerful tool to unravel hepatitis C virus-host interactions within the infectious life cycle. Journal of hepatology.2008 Mar;48(3):523-5.
68.Maissel A MM, Shtutman M, Shahaf G, Livneh E. PKCeta is localized in the Golgi, ER and nuclear envelope and translocates to the nuclear envelope upon PMA activation and serum-starvation:Clb domain and the pseudosubstrate containing fragment target PKCeta to the Golgi and the nuclear envelope. Cell Signal. 2006; 18(8):1127-39.
69.Osada S, Mizuno K, Saido TC, Akita Y, Suzuki K, Kuroki T, et al. A phorbol ester receptor/protein kinase, nPKC eta, a new member of the protein kinase C family predominantly expressed in lung and skin. The Journal of biological chemistry.1990 Dec 25;265(36):22434-40.
70.Greif H, Ben-Chaim J, Shimon T, Bechor E, Eldar H, Livneh E. The protein kinase C-related PKC-L(eta) gene product is localized in the cell nucleus. Molecular and cellular biology.1992 Mar; 12(3):1304-11.
71.Uht RM AS, Martin PM, Riggan AE, Hussaini IM. The protein kinase C-eta isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway. Oncogene.2007 26(20):2885-93.
72.Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, et al. A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nature genetics.2007 Feb;39(2):212-7.
73.Takata Y, Hamada D, Miyatake K, Nakano S, Shinomiya F, Scafe CR, et al. Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme and rheumatoid arthritis in the Japanese population. Arthritis and rheumatism.2007 Jan;56(1):30-42.
74.Aeder SE MP, Soh JW, Hussaini IM. PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene.2004 Dec 2;;23(56):9062-9.
75.Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell.2000 Oct 13;103(2):239-52.
76.Shaulian E, Karin M. AP-1 in cell proliferation and survival. Oncogene.2001 Apr 30;20(19):2390-400.
77.Andrisani OM, Barnabas S. The transcriptional function of the hepatitis B virus X protein and its role in hepatocarcinogenesis (Review). International journal of oncology.1999 Aug;15(2):373-9.
78.Arbuthnot P, Capovilla A, Kew M. Putative role of hepatitis B virus X protein in hepatocarcinogenesis:effects on apoptosis, DNA repair, mitogen-activated protein kinase and JAK/STAT pathways. Journal of gastroenterology and hepatology.2000 Apr;15(4):357-68.
79.Maguire HF, Hoeffler JP, Siddiqui A. HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions. Science (New York, NY.1991 May 10;252(5007):842-4.
60.Benn J, Schneider RJ. Hepatitis B virus HBx protein activates Ras-GTP complex formation and establishes a Ras, Raf, MAP kinase signaling cascade. Proceedings of the National Academy of Sciences of the United States of America.1994 Oct 25;91(22):10350-4.
81.HJ. LYKSK. Phosphorylation of purified recombinant hepatitis B virus·X protein by mitogen activated protein kinase and Protein kinase C in vitro..J virol Methods.2001;95(1-2):1-10.
82.Binetruy B, Smeal T, Karin M. Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. Nature.1991 May 9;351(6322):122-7.
83.R HFK. Hepatitis B virus tranac fiptional ac tivators:mechanisms and possible role in oncngenesis.. J Viral Hepat.1996;3(3):109-21.
84.Ye L, Qi J, Li G, Tao D, Song S. The effect of HBx gene on the apoptosis of hepatic cells. Journal of Huazhong University of Science and Technology Medical sciences= Hua zhong ke ji da xue xue bao Yi xue Ying De wen ban= Huazhong keji daxue xuebao.2007 Apr;27(2):167-9.
85.Zhou MX, Watabe M, Watabe K. The X-gene of human hepatitis B virus transactivates the c-jun and alpha-fetoprotein genes. Archives of virology. 1994;134(3-4):369-78.
1. Bartel DP. MicroRNAs:genomics, biogenesis, mechanism, and function. Cell. 2004 Jan 23; 116(2):281-97.
2. Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell.2005 Dec 16;123(6):1133-46.
3. Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, et al. The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science (New York, NY.2005 Dec 16;310(5755):1817-21.
4. Cullen BR. Transcription and processing of human microRNA precursors. Molecular cell.2004 Dec 22;16(6):861-5.
5. Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA (New York, NY. 2004 Dec;10(12):1957-66.
6. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase Ⅱ. The EMBO journal.2004 Oct 13;23(20):4051-60.
7. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature.2004 Nov 11;432(7014):231-5.
8. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature.2004 Nov 11;432(7014):235-40.
9. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & development.2003 Dec 15;17(24):3011-6.
10. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science (New York, NY.2004 Jan 2;303(5654):95-8.
11. Zeng Y, Cullen BR. Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic acids research.2004;32(16):4776-85.
12. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature.2005 Aug 4;436(7051):740-4.
13. Maniataki E, Mourelatos Z. A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Genes & development.2005 Dec 15;19(24):2979-90.
14. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science (New York, NY. 2004 Sep 3;305(5689):1437-41.
15. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNA and siRNAs. Molecular cell. 2004 Jul 23; 15(2):185-97.
16. Schwarz DS, Hutvagner G, Haley B, Zamore PD. Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. Molecular cell. 2002 Sep;10(3):537-48.
17. Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science (New York, NY.2002 Sep 20;297(5589):2056-60.
18. Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proceedings of the National Academy of Sciences of the United States of America.2003 Aug 19;100(17):9779-84.
19. Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA. Science (New York, NY.2004 Apr 23;304(5670):594-6.
20. Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental biology.1999 Dec 15;216(2):671-80.
21. Zeng Y, Wagner EJ, Cullen BR. Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Molecular cell.2002 Jun;9(6):1327-33.
22. Doench JG, Petersen CP, Sharp PA. siRNAs can function as miRNA. Genes & development.2003 Feb 15;17(4):438-42.
23. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature.2003 Sep 25;425(6956):415-9.
24. Zeng Y, Cullen BR. Sequence requirements for micro RNA processing and function in human cells. RNA (New York, NY.2003 Jan;9(1):112-23.
25. Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, et al. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS pathogens.2006 Mar;2(3):e23.
26. Grundhoff A, Sullivan CS, Ganem D. A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. RNA (New York, NY.2006 May;12(5):733-50.
27. Grey F, Antoniewicz A, Allen E, Saugstad J, McShea A, Carrington JC, et al. Identification and characterization of human cytomegalovirus-encoded microRNAs. Journal of virology.2005 Sep;79(18):12095-9.
28. Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grasser FA, et al. Identification of microRNAs of the herpesvirus family. Nature methods.2005 Apr;2(4):269-76.
29. Fraser NW, Block TM, Spivack JG. The latency-associated transcripts of herpes simplex virus:RNA in search of function. Virology.1992 Nov; 191(1):1-8.
30. Branco FJ, Fraser NW. Herpes simplex virus type 1 latency-associated transcript expression protects trigeminal ganglion neurons from apoptosis. Journal of virology. 2005 Jul;79(14):9019-25.
31. Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science (New York, NY.2004 Apr 30;304(5671):734-6.
32. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proceedings of the National Academy of Sciences of the United States of America; 2005. p.5570-5.
33. Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature.2005 Jun 2;435(7042):682-6.
34. Mathews MB, Shenk T. Adenovirus virus-associated RNA and translation control. Journal of virology.1991 Nov;65(11):5657-62.
35. Thimmappaya B, Weinberger, C, Schneider, R.J. & Shenk,. Adenovirus VA1 RNA is required for efficient translation of viral mRNAs at late times after infection. Cell.1982;31,:543-51.
36. Gwizdek Cea. Terminal minihelix, a novel RNA motif that directs polymerase III transcripts to the cell cytoplasm. J Biol Chem 2001;276:25910-8.
37. Cuddihy AR, et al.. The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro.. Oncogene.1999; 18:2690-702.
38. Williams BR. PKR; a sentinel kinase for cellular stress. Oncogene.1999(18): 6112-20.
39. Zhang F, et al. Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop.. J Biol Chem.2001;276:24946-58.
40. Sano M, Kato Y, Taira K. Sequence-specific interference by small RNAs derived from adenovirus VAI RNA. FEBS letters.2006 Mar 6;580(6):1553-64.
41. Bennasser Y, Le SY, Yeung ML, Jeang KT. HIV-1 encoded candidate micro-RNAs and their cellular targets. Retrovirology.2004; 1:43.
42. Ouellet DL, I. Plante, et al. IO. "." Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. Nucleic Acids Res. 2008.
43. Omoto S, Ito M, Tsutsumi Y, Ichikawa Y, Okuyama H, Brisibe EA, et al. HIV-1 nef suppression by virally encoded microRNA. Retrovirology.2004; 1:44.
44. Cai X, Cullen BR. Transcriptional origin of Kaposi's sarcoma-associated herpesvirus microRNAs. Journal of virology.2006 Mar;80(5):2234-42.
45. Andersson MGea. Suppression of RNA interference by adenovirus virus-associated RNA. J Virol 2005;79:9556-65
46. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proceedings of the National Academy of Sciences of the United States of America.2005 Apr 12;102(15):5570-5.
47. Samols MA, Hu J, Skalsky RL, Renne R. Cloning and identification of a microRNA cluster within the latency-associated region of Kaposi's sarcoma-associated herpesvirus. Journal of virology.2005 Jul;79(14):9301-5.
48. Barth S, Pfuhl T, Mamiani A, Ehses C, Roemer K, Kremmer E, et al. Epstein-Barr virus-encoded micro RNA miR-BART2 down-regulates the viral DNA polymerase BALF5. Nucleic acids research.2008 Feb;36(2):666-75.
49. Tortorella D, Gewurz, B.E., Furman, M.H., Schust, D.J. & Ploegh, H.L. Viral subversion of the immune system. Annu Rev Immunol 2000(18):861-926
50. Katze MG, He Y, Gale M, Jr. Viruses and interferon:a fight for supremacy. Nature reviews.2002 Sep;2(9):675-87.
51. Macrae AI, Dutia BM, Milligan S, Brownstein DG, Allen DJ, Mistrikova J, et al. Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis. Journal of virology.2001 Jun;75(11):5315-27.
52. Omoto S, Fujii YR. Regulation of human immunodeficiency virus 1 transcription by nef micro RN A. The Journal of general virology.2005 Mar;86(Pt 3):751-5.
53. Samols MA, Skalsky RL, Maldonado AM, Riva A, Lopez MC, Baker HV, et al. Identification of cellular genes targeted by KSHV-encoded microRNAs. PLoS pathogens.2007 May 11;3(5):e65.
54. Murphy E, Vanicek J, Robins H, Shenk T, Levine AJ. Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency. Proceedings of the National Academy of Sciences of the United States of America.2008 Apr 8;105(14):5453-8.
55. Couturier JP, Root-Bernstein RS. HIV may produce inhibitory microRNAs (miRNA) that block production of CD28, CD4 and some interleukins. Journal of theoretical biology.2005 Jul 21;235(2):169-84.
56. Cui C, Griffiths A, Li G, Silva LM, Kramer MF, Gaasterland T, et al. Prediction and identification of herpes simplex virus 1-encoded microRNAs. Journal of virology. 2006Jun;80(11):5499-508.
57. Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature.2006 Jul 6;442(7098):82-5.
58. Kim do N, Chae HS, Oh ST, Kang JH, Park CH, Park WS, et al. Expression of viral microRNAs in Epstein-Barr virus-associated gastric carcinoma. Journal of virology.2007 Jan;81(2):1033-6.
59. Stern-Ginossar N, Elefant N, Zimmermann A, Wolf DG, Saleh N, Biton M, et al. Host immune system gene targeting by a viral miRNA. Science (New York, NY. 2007 Jul 20;317(5836):376-81.
60. Gitlin L, Andino R. Nucleic acid-based immune system:the antiviral potential of mammalian RNA silencing. Journal of virology.2003 Jul;77(13):7159-65.
61. Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, et al. A cellular microRNA mediates antiviral defense in human cells. Science (New York, NY.2005 Apr 22;308(5721):557-60.
62. Linial ML. Foamy viruses are unconventional retroviruses. Journal of virology. 1999 Mar;73(3):1747-55.
63. Robinson Triboulet BM, Yea-Lin,Christine Chable-Bessia,. Suppression of miRNA-silencing pathway by HIV-1 during virus replication. Science. 2007;315(16):1579-82.
64. Hariharan M, Scaria V, Pillai B, Brahmachari SK. Targets for human encoded microRNAs in HIV genes. Biochemical and biophysical research communications. 2005 Dec 2;337(4):1214-8.
65. Yeung ML, Bennasser Y, Myers TG, Jiang G, Benkirane M, Jeang KT. Changes in microRNA expression profiles in HIV-1-transfected human cells. Retrovirology. 2005;2:81.
66. Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, et al. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+T lymphocytes. Nature medicine.2007 Oct;13(10):1241-7.
67. Scaria V, Hariharan M, Maiti S, Pillai B, Brahmachari SK. Host-virus interaction: a new role for microRNAs. Retrovirology.2006;3:68.
68. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science (New York, NY. 2005 Sep 2;309(5740):1577-81.
69. Ikeda M, Yi M, Li K, Lemon SM. Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells. Journal of virology.2002 Mar;76(6):2997-3006.
70. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell metabolism.2006 Feb;3(2):87-98.
71. Kapadia SB, and F. V. Chisari. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids.. Proc Natl AcadSci 2005(102):2561-6.
72. Murakami Y, Yasuda T, Saigo K, Urashima T, Toyoda H, Okanoue T, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene.2006 Apr 20;25(17):2537-45.