Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpes simplex virus type 1 establishes latent infection in trigeminal ganglia of mice infected via the eye. A family of three colinear viral transcripts (LATs), 2.0, 1.5, and 1.45 kb, is present in latently infected ganglia. To characterize these LATs, lambda gt10 cDNA libraries were constructed with RNAs isolated from the trigeminal ganglia of latently infected mice. A series of recombinant bacteriophage were isolated containing cDNA inserts covering 1.7 kb of the 2.0-kb LAT. Splice junctions of the smaller LATs and the 3' end of the 2.0-kb LAT were identified by sequence analysis of RNA polymerase chain reaction products. No splice acceptor site, which does not support the hypotheses that the 2.0-kb LAT is an intron. However, the data are consistent with the possibility of a short leader sequence or multiple LAT transcription start sites. To generate the smaller 1.5- and 1.45-kb LATs, there is a 559-nucleotide intron spliced from the 2.0-kb LAT in strain F and a 556-nucleotide intron in strain 17+. The nucleotide sequences at the 5' and 3' ends of these introns are characteristic of spliced transcripts from eukaryotic protein-encoding genes, with one significant difference; i.e., the 5' end of the LAT intron is GC instead of the consensus sequence GT. This splice donor sequence is conserved in herpes simplex virus type 1 strains F, 17+, and KOS. Processing of the 2.0-kb LAT to form the spliced LATs preserves two open reading frames (ORFs) at the 3' end of the LATs; no new ORFs are created. Splicing of the LATs positions a 276-nucleotide leader sequence close to these ORFs and removes an intron that inhibits their translation in vitro. The novel 5' structure of the intron within the 2.0-kb LAT may be part of a control mechanism for transcription processing that results in splicing of the LATs only in sensory neurons during latent infection and reactivation but not during the viral replication cycle.
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PMID:Identification of a novel latency-specific splice donor signal within the herpes simplex virus type 1 2.0-kilobase latency-associated transcript (LAT): translation inhibition of LAT open reading frames by the intron within the 2.0-kilobase LAT. 165 75

Nuclear run-on assays revealed extensive transcription of the Epstein-Barr virus genome during latent infection in in vitro-infected human fetal lymphoblastoid cells (IB-4). The EBER genes were the most heavily transcribed viral genes in these cells. Their transcription was partially inhibited in the presence of 1 microgram of alpha-amanitin per ml and fully inhibited at 100 micrograms/ml, consistent with RNA polymerase III transcription. All other transcription was inhibited at 1 microgram of alpha-amanitin per ml, consistent with RNA polymerase II sensitivity to alpha-amanitin. Other than EBER transcription, almost no transcription occurred from the U1 region. Specifically, no transcription was detected from the U1 latent promoter. RNA polymerase II transcription was highest in IR1, extending rightward through U2 and IR2 into the U3 domain and gradually decreased, but was measurable throughout the rest of the genome. This is consistent with EBNA gene transcription initiation within IR1. The higher level of transcription of the IR1 and U2 domains, which encode EBNA-LP and EBNA-2, as opposed to the domains which encode EBNA-3A, EBNA-3B, or EBNA-3C or EBNA-1, correlated with a higher level of EBNA-LP/EBNA-2 mRNA. Transcription extended through U4 into U5, even though no known latent-gene mRNAs are expressed from U4 downstream of the EBNA-1 open reading frame. This may result from inefficient termination of EBNA gene transcription. Leftward transcription from the latent membrane protein promoter was lower than EBNA transcription, although the latent membrane protein mRNA was the most abundant of the latent-gene mRNAs, indicating that this mRNA is more efficiently processed or has a longer half-life. Although transcription was detected from the DL strong early promoters and to a lesser extent from other early promoters, early mRNAs were less abundant than EBNA mRNAs or undetectable, suggesting that there may be posttranscriptional as well as transcriptional control over early mRNA expression in these latently infected cells.
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PMID:Transcription of the Epstein-Barr virus genome during latency in growth-transformed lymphocytes. 215 49

Following infection of cells by herpes simplex virus, the cell nucleus is subverted for transcription and replication of the viral genome and assembly of progeny nucleocapsids. The transition from host to viral transcription involves viral proteins that influence the ability of the cellular RNA polymerase II to transcribe a series of viral genes. The regulation of RNA polymerase II activity by viral gene products seems to occur by several different mechanisms: (1) viral proteins complex with cellular proteins and alter their transcription-promoting activity (e.g., alpha TIF), (2) viral proteins bind to specific DNA sequences and alter transcription (e.g., ICP4), and (3) viral proteins affect the posttranslational modification of viral or cellular transcriptional regulatory proteins (e.g., possibly ICP27). Thus, HSV may utilize several different approaches to influence the ability of host-cell RNA polymerase II to transcribe viral genes. Although it is known that viral transcription uses the host-cell polymerase II, it is not known whether viral infection causes a change in the structural elements of the nucleus that promote transcription. In contrast, HSV encodes a new DNA polymerase and accessory proteins that complex with and reorganize cellular proteins to form new structures where viral DNA replication takes place. HSV may encode a large number of DNA replication proteins, including a new polymerase, because it replicates in resting cells where these cellular gene products would never be expressed. However, it imitates the host cell in that it localizes viral DNA replication proteins to discrete compartments of the nucleus where viral DNA synthesis takes place. Furthermore, there is evidence that at least one specific viral gene protein can play a role in organizing the assembly of the DNA replication structures. Further work in this system may determine whether assembly of these structures is essential for efficient viral DNA replication and if so, why assembly of these structures is necessary. Thus, the study of the localization and assembly of HSV DNA replication proteins provides a system to examine the mechanisms involved in morphogenesis of the cell nucleus. Therefore, several critical principles are apparent from these discussions of the metabolism of HSV transcription and DNA replication. First, there are many ways in which the activity of RNA polymerase II can be regulated, and HSV proteins exploit several of these in controlling the transcription of a single DNA molecule. Second, the interplay of these multiple regulatory pathways is likely to control the progress of the lytic cycle and may play a role in determining the lytic versus latent infection decision.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of viral and cellular nuclear proteins in herpes simplex virus replication. 255 60

Bovine herpesvirus 1 (BHV-1) establishes a latent infection in sensory ganglionic neurons of infected animals. Expression of latency-related (LR) gene products is controlled by a 980-bp fragment (LR promoter). DNA sequence analysis revealed that two major open reading frames (ORFs) are in the LR gene. Antibodies directed against both ORFs were generated in rabbits by using synthetic peptides. Antibody P2, which is directed to sequences near the amino terminus of ORF 2, recognized a 41-kDa protein in lytically infected cells, suggesting that ORF 2 encodes a protein. When the LR gene was inserted into a mammalian expression vector and subsequently transfected into COS-7 cells, a 41-kDa protein was detected by use of silver-stained sodium dodecyl sulfate-polyacrylamide gels and by the P2 antibody. In contrast, this protein was not detected in mock-transfected cells. Deletion of DNA sequences containing ORF 2 blocked synthesis of the 41-kDa protein in COS-7 cells. Reverse transcriptase-mediated PCRs indicated that splicing occurs near the C terminus of ORF 2. Further studies indicated that LR RNA was alternatively spliced in latently infected cattle and that a fraction of LR RNA was poly(A)+. Taken together, these studies suggested that a spliced LR transcript has the potential to encode a 41-kDa protein.
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PMID:Identification of gene products encoded by the latency-related gene of bovine herpesvirus 1. 763 78

Herpes simplex virus type 1 (HSV-1) establishes latent infection in the sensory ganglia. To investigate the process of reactivation from latency, we used the RNA polymerase chain reaction (RNA-PCR) to detect the expression of several HSV genes. BALB/c mice were inoculated in the anterior ocular chamber with HSV-1 strain KOS and the trigeminal ganglia were examined at least 8 weeks after inoculation. Latency-associated transcripts (LATs) were found in the latently infected ganglia and remained detectable 120 h after explantation. Besides LATs, we detected transcripts for infected cell protein 0 (ICP0) (Vmw110) 24 h after explantation, but RNAs encoding ICP4 (Vmw175), ICP27, thymidine kinase and VP16 (ICP25; Vmw65) remained undetectable for 120 h after explantation. Following in vivo reactivation of HSV-1 by administration of cyclophosphamide and dexamethasone, all viral transcripts including ICP0 RNA became detectable. The RNA-PCR enabled us to detect ICP0 RNA much earlier than has been previously reported in studies using the Northern blot technique and has laid a foundation for further study of viral and cellular transcripts during reactivation. Our results suggest that the process of reactivation of HSV-1 from trigeminal ganglia may be divided into at least two steps: (i) initiation of ICP0 gene transcription and (ii) detectable transcription of the other genes. The second step may be regulated in part by the host immune system, since cyclophosphamide and dexamethasone administration enabled the detection of several viral transcripts.
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PMID:Detection of herpes simplex virus type 1-encoded RNA by polymerase chain reaction: different pattern of viral RNA detection in latently infected murine trigeminal ganglia following in vitro or in vivo reactivation. 812 62

The development of herpes simplex virus as a vector for neuronal gene delivery is dependent upon the identification and characterization of promoter elements capable of driving long-term expression during latency. The majority of RNA polymerase II (pol II) promoters studied are active during acute infection but silenced during latency. In order to investigate the potential of a murine RNA polymerase I (pol I) promoter to drive reporter gene expression during lytic and latent infection, we describe the construction and characterization of two recombinant viruses; SC16 LAT neo and SC16 US5 neo. These viruses contain a pol I-encephalomyocarditis virus internal ribosome entry site (EMCV IRES)-neomycin phosphotransferase gene (neoR) cassette inserted into the non-essential major latency associated transcript (LAT) and US5 regions respectively. Pol I promoter activity could be detected in the rodent BHK cell line, but not the primate derived Vero cell line-- consistent with the known species specificity of such promoters. This activity was specific to a virus containing an active pol I promoter. However, in situ hybridization analyses of latently infected cervical dorsal root ganglia failed to detect pol I mediated transcription of the reporter gene indicating that the murine pol I promoter is silenced following the establishment of latency. Insertion of the pol I-EMCV IRES-neoR cassette into the major LAT locus resulted in the production of a hybrid LAT transcript during latency which was translocated to the cytoplasm of latently infected neurones.
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PMID:A murine RNA polymerase I promoter inserted into the herpes simplex virus type 1 genome is functional during lytic, but not latent, infection. 888 93

Murine gammaherpesvirus 68 (MHV-68) is a virus of wild rodents and is a convenient small animal model for studies of gammaherpesvirus pathogenesis. We have sequenced 6162 bp at the left end of the MHV-68 genome and identified two unique open reading frames (ORFs) (ORF2 and ORF3) and an ORF (ORF1) which displays similarity to poxvirus members of the serpin family. Interspersed with the ORFs is a family of eight novel tRNA-like sequences sharing tRNA-like predicted secondary structures and RNA polymerase III promoter elements. These sequences are expressed to high levels during lytic infection and are processed into mature tRNAs with post-transcriptionally added 3' CCA termini, indicating their recognition as tRNAs by cellular machinery. Acidic Northern analysis of four tRNAs tested has demonstrated that they are not aminoacylated by aminoacyl-tRNA synthetases present in the infected cell. Thus, it is currently unclear what biological function these uncharged viral tRNA-like sequences may fulfil. In situ hybridization analysis has shown that in addition to being expressed within productively infected tissues during acute stages of infection, the tRNA-like sequences are abundantly expressed within splenic germinal centres of latently infected mice. Therefore, the MHV-68 viral tRNAs represent a marker for latent infection and constitute the first report of tRNA-like sequences encoded by a virus of eukaryotes.
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PMID:Murine gammaherpesvirus 68 encodes tRNA-like sequences which are expressed during latency. 922 45

The human immunodeficiency virus type 1 (HIV-1) Tat protein is essential for viral replication and stimulates transcription of the integrated provirus by recruiting the kinase complex TAK/P-TEFb, composed of cyclin T1 (CycT1) and Cdk9, to the viral TAR RNA element. TAK/P-TEFb phosphorylates the RNA polymerase II complex and stimulates transcriptional elongation. In this report, we investigated the regulation of TAK/P-TEFb in primary human macrophages, a major target cell of HIV infection. While Cdk9 levels remained constant, CycT1 protein expression in freshly isolated monocytes was very low, increased early during macrophage differentiation, and, unexpectedly, decreased to very low levels after about 1 week in culture. The kinase activity of TAK/P-TEFb paralleled the changes in CycT1 protein expression. RNA analysis indicated that the transient induction of CycT1 protein expression involves a posttranscriptional mechanism. In transient transfection assays, the ability of Tat to transactivate the HIV long terminal repeat (LTR) in the late differentiated macrophages was greatly diminished relative to its ability to transactivate the HIV LTR in early differentiated cells, strongly suggesting that CycT1 is limiting for Tat function in late differentiated macrophages. Interestingly, lipopolysaccharide, a component of the cell wall of gram-negative bacteria, reinduced CycT1 expression late in macrophage differentiation. These results raise the possibility that regulation of CycT1 expression may be involved in establishing latent infection in macrophages and that opportunistic infection may reactivate the virus by inducing CycT1 expression.
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PMID:Transient induction of cyclin T1 during human macrophage differentiation regulates human immunodeficiency virus type 1 Tat transactivation function. 1236

Channel catfish virus (CCV) produces an acute haemorrhagic disease in fingerling channel catfish and establishes latent infection in fish that survive the primary infection. This study investigated CCV gene expression in tissues of experimentally infected fish. Reverse transcriptase polymerase chain reaction assays were developed for detection of transcripts expressed by each of the CCV direct repeat region genes in CCV-infected channel catfish ovary cells and in tissues of infected fish. Immediate-early, early and late gene transcripts were detected in the blood, brain, kidney and liver tissues of acutely infected catfish demonstrating active viral replication in multiple tissues during the early stages of CCV infection. However, there was no evidence for viral replication by 24 days post-infection in tissues of fish that survived the acute disease. Viral latency-associated transcripts encoded by CCV direct repeat genes were not detected in latently infected catfish. The results of this study provide a foundation for further studies to investigate the molecular basis of CCV pathogenesis and latency.
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PMID:Channel catfish virus gene expression in experimentally infected channel catfish, Ictalurus punctatus (Rafinesque). 1451 73

Human immunodeficiency virus type 1 (HIV-1) is able to establish a latent infection during which the integrated provirus remains transcriptionally silent. In response to specific stimuli, the HIV-1 long terminal repeat (LTR) is highly activated, enhancing both transcriptional initiation and elongation. Here, we have identified a specific binding sequence of the nuclear NF-kappaB-repressing factor (NRF) within the HIV-1 LTR. The aim of this work was to define the role of NRF in regulating the LTR. Our data show that the endogenous NRF is required for transcriptional activation of the HIV-1 LTR in stimulated cells. In unstimulated cells, however, NRF inhibits HIV-1 LTR activity at the level of transcription elongation. Binding of NRF to the LTR in unstimulated cells prevents recruitment of elongation factor DRB sensitivity-inducing factor and formation of processive elongation complexes by hyperphosphorylated RNA polymerase II. Our data suggest that NRF interrupts the regulatory coupling of LTR binding factors and transcription elongation events. This inhibitory mechanism might contribute to transcriptional quiescence of integrated HIV-1 provirus.
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PMID:NF-kappaB-repressing factor inhibits elongation of human immunodeficiency virus type 1 transcription by DRB sensitivity-inducing factor. 1610 96


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