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:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The arenaviruses are a group of enveloped viruses having as a unique morphological finding the presence in the virion of granules instead of a defined core. The viruses contain a single-stranded RNA genome, but appreciable amounts of ribosomal-like RNA and 4-6S RNA of host cell origin have been detected. Little information is available on the mode of replication of the viral nucleic acids. A virion-associated RNA-dependent RNA polymerase has been described and there is indirect evidence to suggest that host cell RNA or DNA participates in virus replication. However, the steps in viral RNA synthesis and expression have not yet been elucidated.Pichinde virus contains 2 glycoproteins and 2 polypeptides. Cells infected with Pichinde virus or LCM virus have been shown to produce 2 antigens detectable by immunodiffusion. Both antigens appear to be components of the virion, but the relation between the antigens detected by immunodiffusion and the polypeptides detected by polyacrylamide gel electrophoresis has not yet been clarified.
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PMID:Arenaviruses: purification and physicochemical nature. 108 4

During persistent infection of mouse L cells with strain Armstrong lymphocytic choriomeningitis virus, the latter undergoes characteristic changes, including loss of mouse pathogenicity and failure to form plaques on cultivated cells. We call this virus L(Arm) and have analyzed transcription and translation of its S-RNA, which codes for the viral nucleoprotein (NP) and the glycoprotein precursor (GP-C). In L(Arm) virus-infected L cells, S-RNA and genomic-sized viral complementary S-RNA (VC-S-RNA) were detected and, in addition, considerable quantities of shortened molecules of either species. The cells' content of NP was high, but they contained little GP-C; instead, a viral glycoprotein with MW 65,000 was present. We propose a hypothesis in which it is assumed that along the VC-S-RNA there is more than one recognition site for the viral RNA-dependent RNA polymerase, which leads to the generation of truncated forms of S-RNA, VC-S-RNA, and mRNA for GP-C; this, in turn, results in relative overproduction of NP and relative underproduction of GP-C as well as the emergence of a new form of viral glycoprotein.
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PMID:Mode of replication of lymphocytic choriomeningitis virus in persistently infected cultivated mouse L cells. 169 11

Operator-induced biological contamination in cell cultures is a multifaceted problem involving the unexpected introduction of other animal cells, microbial and viral contaminants. Detailed studies on animal cell cross contaminations have been performed and published. The frequency of detection of problem cultures has been as high as 36% for one service performed in the USA, with interspecific cross contamination accounting for 25% and human intraspecific contamination representing 11%. Awareness of the potential of this problem plus the application of several characterizations are key factors for its control. For example, fluorescent antibody staining, isoenzyme analyses, cytogenetic evaluations and DNA fingerprinting using molecular probes are needed for quality assurance on master seed stocks. Detection of microbial contamination is relatively straightforward, but the prevalence of mycoplasmal infections in cell cultures used in general research is still a significant problem. Detection services report frequencies of infection varying from 10% upwards, depending upon the country and laboratory of origin. The utilization of prescreened reagents and antibiotic-free cultivation, plus the application of improved procedures, such as fluorescent dyes and molecular probes for detection, provide effective means of avoiding mycoplasma infection and facilitating control. For many viruses, the presence of mycoplasma reduces immunoreactivity, suppresses transcriptase and other enzyme activities, reverses viral neutralization etc. The introduction of viral contaminants into cell cultures is perhaps the most problematic, especially where no cytopathic effect is produced. Few cases are documented where technicians infected with specific viruses have introduced these unwittingly into cultures in their care. The potential exists, however, as reports have appeared documenting the considerable stability of rhinoviruses, respiratory syncytial virus, rotaviruses and others, in aerosols on workers' hands and safety hood surfaces. The infection of cell cultures via other contaminated cells or reagents such as sera is a related problem. In this regard, the infection of transplantable tumor cell lines with lymphocytic choriomeningitis virus from host animals led to an outbreak of the disease in medical center personnel. Similar infection of rat cell lines exposed to animals harboring hantaviruses has been reported. Technical staff in US government laboratories have been infected with human immunodeficiency virus produced in cultured cells. Such serious public health hazards warrant repeated emphasis. The use of multiple cell lines in a given laboratory, including cultures known to be virally infected, compounds the problems and necessitates application of preventive methods both to avoid cross-infections and to document freedom from contamination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Operator-induced contamination in cell culture systems. 179 20

We have developed an in vitro assay for the lymphocytic choriomeningitis virus (LCMV) RNA-dependent RNA polymerase with ribonucleoprotein complexes extracted from acutely infected tissue culture cells. The RNA products synthesized in vitro corresponded in size to the full-length genomic L and S RNAs and subgenomic NP and GP mRNAs normally produced in vivo during acute LCMV infection. In a temporal analysis spanning the first 72 h of acute infection, the in vitro polymerase activity of ribonucleoprotein complexes was maximal at 16 h and declined significantly at later times. In contrast, the intracellular levels of the viral L protein (the putative polymerase protein) appeared to be maximal at 48 to 72 h postinfection. Our results suggest that the accumulation of L protein correlates with reduced viral replication and transcription at later times in acute infection and may be involved in the transition from acute to persistent LCMV infection.
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PMID:Detection of virus-specific RNA-dependent RNA polymerase activity in extracts from cells infected with lymphocytic choriomeningitis virus: in vitro synthesis of full-length viral RNA species. 270 71

The complete RNA sequence of the L protein gene of lymphocytic choriomeningitis virus (LCMV) is presented. It is the first L protein sequence to be obtained for the Arenaviridae, a family of single-stranded RNA viruses which includes Lassa fever virus, and the Tacaribe complex viruses such as Pichinde and the Argentine and Bolivian hemorrhagic fever viruses. It is the largest open reading frame on the L RNA spanning 6633 nucleotides and coding for a 2210 amino acid protein with a calculated molecular weight of 254,529. Antipeptide sera identify a gene product encoded on the L RNA: it has a mass of approximately 200,000 Da and is found in virions and ribonucleoprotein complexes from infected cells (M. Singh, F. Fuller-Pace, M. J. Buchmeier, and P. J. Southern, 1987, Virology, 161, 448-456). Mutations mapped to the L gene affect plaque morphology (Kirk et al., 1980), the lethality of a virulent LCMV strain on guinea pigs (Y. Riviere, R. Ahmed, P. J. Southern, M. J. Buchmeier, and M. B. A. Oldstone, 1985, J. Virol., 55, 704-709), and the ability of a variant strain of LCMV to suppress the cytotoxic T-cell response and initiate persistent infection (M. Salvato, E. Shimomaye, P. Southern, and M. B. A. Oldstone, 1988, Virology, 164, 517-522; Ahmed et al., 1988). All of these phenotypes indicate that the viral genes on the L strand are critical elements controlling virus replication and the pattern of LCMV infection. The L gene sequence encodes a viral polymerase although this protein bears little resemblance to the published sequences of other RNA virus polymerases. Therefore the LCMV polymerase likely represents a distinct category of viral transcriptase.
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PMID:The primary structure of the lymphocytic choriomeningitis virus L gene encodes a putative RNA polymerase. 270 3

The large (L) RNA segment of Lassa fever virus (LAS) encodes a putative RNA-dependent RNA polymerase (RdRp or L protein). Similar to other arenaviruses, the LAS L protein is encoded on the genome-complementary strand and is predicted to be 2218 amino acids in length (253 kDa). It has an unusually large non-coding region adjacent to its translation start site. The LAS L protein contains six motifs of conserved amino acids that have been found among arenavirus L proteins and core RdRp of other segmented negative-stranded (SNS) viruses (Arena-, Bunya- and Orthomyxoviridae). Phylogenetic analyses of the RdRp of 20 SNS viruses reveals that arenavirus L proteins represent a distinct cluster divided into LAS-lymphocytic choriomeningitis and Tacaribe-Pichinde virus lineages. Monospecific serum against a synthetic peptide corresponding to the most conserved central domain precipitates a 250 kDa product from LAS and lymphocytic choriomeningitis virus-infected cells.
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PMID:The Lassa fever virus L gene: nucleotide sequence, comparison, and precipitation of a predicted 250 kDa protein with monospecific antiserum. 904 3

Two strains of lymphocytic choriomeningitis virus (LCMV) differ in their ability to cause a lethal disease in outbred guinea pigs: the Armstrong (ARM) strain is not lethal at high doses (10(6) PFU), whereas the WE strain is lethal at less than 10 PFU inoculated intraperitoneally. The high pathogenic potential of LCMV WE has been mapped to the larger (L) of the two genomic RNA segments by genetic reassortment analysis (Riviere, Y., Ahmed, R., Southern, P. J., Buchmeier, M. J. and Oldstone, M. B. A., J. Virol. 55, 704-709, 1985). Here we describe the completed sequence of the LCMV WE L RNA, and its comparison to the L RNA of the non-virulent strain, LCMV ARM. Similar to the L RNA of LCMV ARM, the L RNA of WE is 7.2 kb long and contains two open reading frames (ORFs): the 5" ORF encodes a small RING finger (zinc-binding) protein, p11 Z, and the 3" ORF encodes the putative RNA-dependent RNA polymerase (RdRp or L protein). Comparison of nucleotide sequences for both viruses revealed 84% L RNA homology. At the amino acid level similarity between the two strains is 87% in the Z ORF, and 88% in the RdRp ORF. The most divergent regions are found in the N-terminal parts of the RdRp and Z proteins and are most likely to account for differences in pathogenic potential.
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PMID:Sequence comparison of the large genomic RNA segments of two strains of lymphocytic choriomeningitis virus differing in pathogenic potential for guinea pigs. 985 88

The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) has a bisegmented negative-strand RNA genome. Each segment carries two viral genes in opposite orientation and separated by an intergenic region (IGR). The RNA-dependent RNA polymerase (RdRp) L of LCMV produces subgenomic mRNA and full-length genomic and antigenomic RNA species in two different processes termed transcription and replication, respectively. It is widely accepted that intracellular nucleoprotein (NP) levels regulate these two processes. Intracellular NP levels increase during the course of the infection, resulting in the unfolding of secondary RNA structures within the IGR. Structure-dependent transcription termination at the IGR is thereby attenuated, promoting replication of genome and antigenome RNA species. To test this hypothesis, we established a helper-virus-free minigenome (MG) system where intracellular synthesis of an S segment analogue from a plasmid is driven by RNA polymerase I. Cotransfection with two additional plasmids expressing the minimal viral trans-acting factors L and NP under control of RNA polymerase II allowed for RNA synthesis mediated by the intracellularly reconstituted LCMV polymerase. Both processes, transcription and replication, were strictly dependent on NP. However, both were equally enhanced by incrementally increasing amounts of NP up to levels in the range of those in LCMV-infected cells. Our data are consistent with a central role for NP in transcription and replication of the LCMV genome, but they do not support the participation of NP levels in balancing the two processes.
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PMID:Role of the virus nucleoprotein in the regulation of lymphocytic choriomeningitis virus transcription and RNA replication. 1261 Jan 66

The arenavirus L protein has the characteristic sequence motifs conserved among the RNA-dependent RNA polymerase L proteins of negative-strand (NS) RNA viruses. Studies based on the use of reverse-genetics approaches have provided direct experimental evidence of the key role played by the arenavirus L protein in viral-RNA synthesis. Sequence alignment shows six conserved domains among L proteins of NS RNA viruses. The proposed polymerase module of L is located within its domain III, which contains highly conserved amino acids within motifs designated A and C. We have examined the role of these conserved residues in the polymerase activity of the L protein of the prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), in vivo using a minigenome rescue assay. We show here that the presence of sequence SDD, a characteristic of motif C of segmented NS RNA viruses, as well as the presence of the highly conserved D residue within motif A of L proteins, is strictly required for the polymerase activity of the LCMV L protein. The strong dominant negative phenotype associated with many of the mutants examined and results from coimmunoprecipitation studies provided genetic and biochemical evidence, respectively, for the requirement of the L-L interaction for the polymerase activity of the LCMV L protein.
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PMID:Genetic and biochemical evidence for an oligomeric structure of the functional L polymerase of the prototypic arenavirus lymphocytic choriomeningitis virus. 1589 Sep 65

Arenaviruses exist as viral quasispecies due to the high mutation rates of the low-fidelity viral RNA-dependent RNA polymerase (RdRp). This genomic heterogeneity is advantageous to the population, allowing for adaptation to rapidly changing environments that present varying types and degrees of selective pressure. The significant variation in biological properties observed among lymphocytic choriomeningitis virus (LCMV) strains, the prototypic arenavirus, indicates to what extent a quasis-pecies dynamics may play a role in arenavirus adaptability and pathogenesis. Several aspects of arenavirus variability and its contribution to pathogenesis will be discussed.
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PMID:Arenavirus diversity and evolution: quasispecies in vivo. 1656 4


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