MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of ...MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorigenesis. Recent studies provide clear evidence that miRNAs are abundant in the liver and modulate a diverse spectrum of liver functions. Deregulation of miRNA expression may be a key pathogenetic factor in many liver diseases including viral hepatitis, hepatocellular cancer and polycystic liver diseases. A clearer understanding of the mechanisms involved in miRNA deregulation will offer new diagnostic and therapeutic strategies to treat liver diseases. Moreover, better understanding of miRNA regulation and identification of tissue-specific miRNA targets employing transgenic/knockout models and/or modulating oligonucleotides will improve our knowledge of liver physiology and diseases.展开更多
After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization wi...After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-I infection process begins when the gpl20 subunit of the envelope glycoprotein complex interacts with its receptor（s） on the target cell. The V3 domain of gpl20 is the major determinant of cellular co-receptor binding. According to phenotypic information of HIVol isolates, sequences from the VpU to V3 regions （119 in R5- and 120 X4-tropic viruses; one per patient） were analysed. The binomial correlation phi coefficient was used to assess covariation among VpU and gpl20v3 signatures. Subsequently, average linkage hierarchical agglomerative clustering was performed. Beyond the classical V3 signatures （R5-viruses： SI1, E25D; X4-viruses： SllKR, E25KRQ）, other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. Several statistically significant associations between V3 and VpU mutations were also observed. The dendrogram showed two distinct large clusters： one associated with R5-tropic sequences （bootstrap=0.94）, involving： （a） H13NPv3, E25Dv3, Sllv3, T22Av3 and Q61Hvpu, （b） E25Av3 and L12Fvpu, （c） D44Evpu, R18Qv3 and D80Nvpu; and another associated with X4-tropic sequences （bootstrap=0.97）, involving： （i） E25Iv3 and V10Avpu, （ii） 0-1insVvpc, H13Rv3, I46Lvpc, I30Mv3 and 60-62delvpu, （iii） SllKRv3 and E25KRQv3. Some of these pairs of mutations were encoded always by one specific codon. These data indicate the possible VpU mutational patterns contributing to regulation of HIV-I tropism.展开更多
基金Supported by National Institute of Health grant (R01 AI071321)the Tobacco Settlement Foundation of Nebraska (LB 692)
文摘MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorigenesis. Recent studies provide clear evidence that miRNAs are abundant in the liver and modulate a diverse spectrum of liver functions. Deregulation of miRNA expression may be a key pathogenetic factor in many liver diseases including viral hepatitis, hepatocellular cancer and polycystic liver diseases. A clearer understanding of the mechanisms involved in miRNA deregulation will offer new diagnostic and therapeutic strategies to treat liver diseases. Moreover, better understanding of miRNA regulation and identification of tissue-specific miRNA targets employing transgenic/knockout models and/or modulating oligonucleotides will improve our knowledge of liver physiology and diseases.
文摘After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-I infection process begins when the gpl20 subunit of the envelope glycoprotein complex interacts with its receptor（s） on the target cell. The V3 domain of gpl20 is the major determinant of cellular co-receptor binding. According to phenotypic information of HIVol isolates, sequences from the VpU to V3 regions （119 in R5- and 120 X4-tropic viruses; one per patient） were analysed. The binomial correlation phi coefficient was used to assess covariation among VpU and gpl20v3 signatures. Subsequently, average linkage hierarchical agglomerative clustering was performed. Beyond the classical V3 signatures （R5-viruses： SI1, E25D; X4-viruses： SllKR, E25KRQ）, other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. Several statistically significant associations between V3 and VpU mutations were also observed. The dendrogram showed two distinct large clusters： one associated with R5-tropic sequences （bootstrap=0.94）, involving： （a） H13NPv3, E25Dv3, Sllv3, T22Av3 and Q61Hvpu, （b） E25Av3 and L12Fvpu, （c） D44Evpu, R18Qv3 and D80Nvpu; and another associated with X4-tropic sequences （bootstrap=0.97）, involving： （i） E25Iv3 and V10Avpu, （ii） 0-1insVvpc, H13Rv3, I46Lvpc, I30Mv3 and 60-62delvpu, （iii） SllKRv3 and E25KRQv3. Some of these pairs of mutations were encoded always by one specific codon. These data indicate the possible VpU mutational patterns contributing to regulation of HIV-I tropism.
