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)

Multiple sclerosis (MS) has an unknown cause, but its epidemiology suggests an interplay between environmental factors, possibly including viruses, and genetic components. Endogenous retroviruses (ERVs) are elements of the human genome that potentially may act as either genetic markers for polymorphisms related to MS, or markers of environmental/endogenous stress. Activation of the ERVs HERV-H/RGH, HERV-W and ERV-9 was reported when specific cell types (mainly B cells) from MS patients were cultivated in vitro. Viral RNA from these ERVs has been detected by reverse-transcriptase polymerase chain reaction in sera/plasma and brain tissues from MS patients, although not exclusively from these patients. ERVs play unknown roles in MS: their activation may represent an inflammatory cytokine-mediated epiphenomenon; alternatively, preliminary evidence suggests that specific ERVs may act as auto-, super- or neoantigens with the potential to enhance inflammatory responses or induce autoimmune reactions. ERVs that occur in few copies in the human genome (e.g. ERV-3 and human endogenous retrovirus, HRES-1) may show polymorphic patterns in MS. Studies show that the sequences encoding the envelope protein of ERV-3 are polymorphic to a degree where it becomes impossible to link them with MS. In contrast, the HRES-1 long terminal repeat sequence has a polymorphic pattern with haplotypes characteristic of MS. Haplotypes from non-MS control groups were identical between different topographic areas, but haplotypes from MS patients were different, depending on the population.
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PMID:Endogenous retroviruses and MS: using ERVs as disease markers. 1290 66

Our aim was to isolate and characterize white spot syndrome virus (WSSV)-binding proteins from shrimp. After a blot of shrimp hemocyte membrane proteins was overlaid with a recombinant WSSV envelope protein (rVP28), the reactive bands on the blot were detected using anti-VP28 antibody. Among three membrane-associated molecules identified by liquid chromatography-tandem mass spectrometry, there was a 25-kDa protein that bound to both rVP28 and WSSV. Since it had a primary structure with high homology to the small GTP-binding protein Rab7, we named it Penaeus monodon Rab7 (PmRab7). The full-length PmRab7 cDNA was obtained, and results from a glutathione S-transferase pull-down assay confirmed specific binding to rVP28. Reverse transcriptase PCR analysis revealed PmRab7 expression in many tissues, and real-time PCR analysis revealed that expression was constitutive. Binding of PmRab7 to rVP28 or WSSV occurred in a dose-dependent manner and was inhibited by anti-Rab7 antibody. In an in vivo neutralization assay, the number of dead shrimp after challenge with WSSV plus PmRab7 (15%) or WSSV plus anti-Rab7 antibody (5%) was significantly lower than after challenge with WSSV alone (95%). In contrast to the WSSV-injected group, shrimp injected with WSSV plus PmRab7 or WSSV plus anti-Rab7 showed no WSSV-type histopathology. We conclude that PmRab7 is involved in WSSV infection in shrimp. This is the first study to identify a shrimp protein that binds directly to a major viral envelope protein of WSSV.
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PMID:PmRab7 is a VP28-binding protein involved in white spot syndrome virus infection in shrimp. 1704 Dec 24

The vaccinia viral vector containing T7 promoter was used to construct the expression plasmids carrying HCV structural genes of C, El and E2/NS1. These genes were transiently expressed in mammalian cells in the presence of the T7 RNA polymerase which was provided by the recombinant vaccinia virus vTT7. Expression of mature core protein, envelope protein El and E2 was detected by Western blot using HCV patient sera as the primary antibodies. It was found that the sera from different HCV patients reacted differently with the expressed products, so did the sera collected at different times from the same patient, from whom the HCV structural genes were isolated. Among six mammalian cell lines, Vero and HeLa were the most suitable for the expression of C, El and E2-The recombinant vaccinia viruses have been constructed to constantly produce the C, El and E2 proteins for further research.
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PMID:Expression of structural proteins of hepatitis C virus (HCV) in mammalian cells. 1872 70

There are two recognized poxviruses that are associated with disease in tree squirrels: squirrel fibroma virus (SQFV), Leporipoxvirus, which affects eastern grey squirrels (Sciurus carolinensis) in eastern North America, and squirrelpox virus (SQPV), a member of a newly identified poxvirus genus, which affects European red squirrels (Sciurus vulgaris) in the United Kingdom. In August 2008, a cutaneous poxvirus-associated disease was identified in a North American red squirrel (Tamiasciurus hudsonicus) from the Yukon Territory, Canada. The gross and microscopic appearance of the skin lesions was more consistent with SQPV than SQFV, and electron microscopy revealed poxvirions only within epithelial cells. Polymerase chain reaction (PCR) was used to identify poxvirus core protein encoding DNA in skin samples, and phylogenetic analysis showed that the inferred amino acid sequence was distinct from all other poxvirus species for which the core protein gene has been sequenced, including those of the genus Leporipoxvirus. Although the core protein sequence of SQPV was not available, comparison of the constructed phylogenetic tree to other published trees, based on major outer envelope proteins, revealed that the identified sequence occupies a position similar to SQPV in terms of its relationship to other poxviruses. However, PCR primers designed to amplify gene sequences encoding the SQPV major envelope protein and RNA polymerase did not amplify any sequences from infected tissues. These findings suggest that the virus present in this squirrel is a novel poxvirus of North American red squirrels. To our knowledge, this is the first case of poxvirus infection in Canadian squirrels outside of Ontario.
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PMID:Poxvirus infection in an American red squirrel (Tamiasciurus hudsonicus) from northwestern Canada. 1990 87

In this study, we used an RNA polymerase I (Pol I) transcription system for development of a reverse genetics protocol to produce hepatitis C virus (HCV), which is an uncapped positive-strand RNA virus. Transfection with a plasmid harboring HCV JFH-1 full-length cDNA flanked by a Pol I promoter and Pol I terminator yielded an unspliced RNA with no additional sequences at either end, resulting in efficient RNA replication within the cytoplasm and subsequent production of infectious virions. Using this technology, we developed a simple replicon trans-packaging system, in which transient transfection of two plasmids enables examination of viral genome replication and virion assembly as two separate steps. In addition, we established a stable cell line that constitutively produces HCV with a low mutation frequency of the viral genome. The effects of inhibitors of N-linked glycosylation on HCV production were evaluated using this cell line, and the results suggest that certain step(s), such as virion assembly, intracellular trafficking, and secretion, are potentially up- and downregulated according to modifications of HCV envelope protein glycans. This Pol I-based HCV expression system will be beneficial for a high-throughput antiviral screening and vaccine discovery programs.
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PMID:Production of infectious hepatitis C virus by using RNA polymerase I-mediated transcription. 2023 83

Entry inhibitor is a new class of drugs that target the viral envelope protein. This region is variable; hence resistance to these drugs may be present before treatment. The aim of this study was to analyze the frequency of patients failing treatment with transcriptase reverse and protease inhibitors that would respond to the entry inhibitors Enfuvirtide, Maraviroc, and BMS-806. The study included 100 HIV-1 positive patients from one outpatient clinic in the city of Sao Paulo, for whom a genotype test was requested due to treatment failure. Proviral DNA was amplified and sequenced for regions of gp120 and gp41. A total of 80 could be sequenced and from those, 73 (91.3%), 5 (6.3%) and 2 (2.5%) were classified as subtype B, F, and recombinants (B/ F and B/C), respectively. CXCR4 co-receptor use was predicted in 30% of the strains. Primary resistance to Enfuvirtide was found in 1.3%, following the AIDS Society consensus list, and 10% would be considered resistant if a broader criterion was used. Resistance to BMS-806 was higher; 6 (7.5%), and was associated to non-B strains. Strikingly, 27.5% of samples harbored one or more mutation among A316T, I323V, and S405A, which have been related to decreased susceptibility of Maraviroc; 15% of them among viruses predictive to be R5. A more common mutation was A316T, which was associated to the Brazilian B strain harboring the GWGR motif at the tip of V3 loop and their derivative sequences. These results may be impact guidelines for genotype testing and treatment in Brazil.
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PMID:Evaluation of primary resistance to HIV entry inhibitors among brazilian patients failing reverse transcriptase/protease inhibitors treatment reveal high prevalence of maraviroc resistance-related mutations. 2097

Gene order is often highly conserved within taxonomic groups, such that organisms with rearranged genomes tend to be less fit than wild type gene orders, and suggesting natural selection favors genome architectures that maximize fitness. But it is unclear whether rearranged genomes hinder adaptability: capacity to evolutionarily improve in a new environment. Negative-sense non-segmented RNA viruses (order Mononegavirales) have specific genome architecture: 3' UTR - core protein genes - envelope protein genes - RNA-dependent RNA-polymerase gene - 5' UTR. To test how genome architecture affects RNA virus evolution, we examined vesicular stomatitis virus (VSV) variants with the nucleocapsid (N) gene moved sequentially downstream in the genome. Because RNA polymerase stuttering in VSV replication causes greater mRNA production in upstream genes, N gene translocation toward the 5' end leads to stepwise decreases in N transcription, viral replication and progeny production, and also impacts the activation of type 1 interferon mediated antiviral responses. We evolved VSV gene-order variants in two prostate cancer cell lines: LNCap cells deficient in innate immune response to viral infection, and PC-3 cells that mount an IFN stimulated anti-viral response to infection. We observed that gene order affects phenotypic adaptability (reproductive growth; viral suppression of immune function), especially on PC-3 cells that strongly select against virus infection. Overall, populations derived from the least-fit ancestor (most-altered N position architecture) adapted fastest, consistent with theory predicting populations with low initial fitness should improve faster in evolutionary time. Also, we observed correlated responses to selection, where viruses improved across both hosts, rather than suffer fitness trade-offs on unselected hosts. Whole genomics revealed multiple mutations in evolved variants, some of which were conserved across selective environments for a given gene order.
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PMID:Genome rearrangement affects RNA virus adaptability on prostate cancer cells. 2588 1

West Nile virus is globally wide-spread and causes significant disease in humans and animals. The evolution of West Nile virus Kunjin subtype in Australia (WNVKUN) was investigated using archival samples collected over a period of 50 years. Based on the pattern of fixed amino acid substitutions and time-stamped molecular clock analyses, a single long-term lineage (or topotype) was inferred. This implies that a bottleneck exists such that regional strains eventually die out and are replaced with strains from a single source. This was consistent with current hypotheses regarding the distribution of WNVKUN, whereby the virus is enzootic in northern Australia and is disseminated to southern states by water-birds or mosquitoes after flooding associated with above average rainfall. In addition, two previous amino acid changes associated with pathogenicity, an N-Y-S glycosylation motif in the envelope protein and a phenylalanine at amino acid 653 in the RNA polymerase, were both detected in all isolates collected since the 1980s. Changes primarily occurred due to stochastic drift. One fixed substitution each in NS3 and NS5, subtly changed the chemical environment of important functional groups, and may be involved in fine-tuning RNA synthesis. Understanding these evolutionary changes will help us to better understand events such as the emergence of the virulent strain in 2011.
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PMID:Archival Isolates Confirm a Single Topotype of West Nile Virus in Australia. 2790 66


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