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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that human endogenous retroviruses (HERVs) play a role in autoimmune diseases is subject to increasing attention. HERVs represent both putative susceptibility genes and putative pathogenic viruses in the immune-mediated neurological disease multiple sclerosis (MS). Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level. Two types of sequences, HERV-H and HERV-W, have been reported. No known HERV-H or HERV-W copy contains complete ORFs in all prerequisite genes, although several copies have coding potential, and several such sequences are specifically activated in MS, apparently resulting in the production of complete, competent virions. Increased antibody reactivity to specific Gammaretroviral HERV epitopes is found in MS serum and CSF, and cell-mediated immune responses have also been reported. Further, HERV-encoded proteins can have neuropathogenic effects. The activating factor(s) in the process resulting in protein or virion production may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS.
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PMID:Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses. 1578 88

Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused by Sarcocystis neurona. Recently, a 29-kDa surface antigen from S. neurona merozoites was identified as being highly immunodominant on a Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. In a previous study, cell-mediated immune responses to SnSAG1 were shown to be statistically significantly reduced in horses with EPM in comparison to EPM-negative control horses. It therefore appears as though the parasite is able to induce immunosuppression towards parasite-derived antigens as parasite-specific responses are decreased. Isolated peripheral blood lymphocytes from 21 EPM (cerebrospinal fluid [CSF] Western blot)-negative horses with no clinical signs and 21 horses with clinical signs of EPM (CSF Western blot positive) were cocultured with SnSAG1 for 48 and 72 h, and the effect on cytokine production was investigated by means of reverse transcriptase PCR. Cytokines assayed include gamma interferon (IFN-gamma), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, and IL-6. beta-Actin was used as the housekeeping gene. A Wilcoxon signed-rank test of the findings indicated that there was a statistically significant decrease in IFN-gamma production after 48 h in culture for samples from horses with clinical disease. There was also a statistically significant increase in IL-4 production after 72 h in culture for samples from horses with EPM. These results further support the notion that this parasite is able to subvert the immune system in horses with clinical disease.
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PMID:Cytokine gene expression in response to SnSAG1 in horses with equine protozoal myeloencephalitis. 1587 26

A review of mumps outbreaks among both non-vaccinated and vaccinated children and young adults in the East Bohemian region in 2003-2005 is presented. A significant increase in mumps cases was observed over this period. The clinical diagnosis was confirmed serologically by ELISA detection of IgM antibodies and/or IgG seroconversion and increased levels of IgG antibodies. A reverse transcriptase nested PCR was introduced for direct detection of mumps virus RNA from clinical specimens (nasopharyngeal secretion, saliva, CSF and serum). The isolated RNA will be stored for further analysis and mumps virus genotyping attempts, helpful in tracing the virus circulation in the East Bohemia region. Possible causes of the recent significant increase in mumps cases among the vaccinated population in the Czech Republic are discussed.
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PMID:[Mumps--a reemerging infection? The current incidence of mumps in the East Bohemian region in the Czech Republic]. 1735 87

Reverse transcriptase has been detected in the serum of HIV-negative patients with amyotrophic lateral sclerosis (ALS). An ALS-like disorder in HIV-positive patients can remit with antiretroviral therapy. Using the product enhanced assay technique, we measured reverse transcriptase activity in the serum and CSF of 23 HIV-negative patients with ALS and 21 neurologic disease controls. Results for CSF were not significant, whereas reverse transcriptase was detected in 56% of ALS sera vs 19% of controls.
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PMID:A controlled study of reverse transcriptase in serum and CSF of HIV-negative patients with ALS. 1753 52

Granulocyte macrophage-colony stimulating factor (GM-CSF) has immuno-stimulatory effects. We hypothesized that GM-CSF plays an important role both in lipopolysaccharide (LPS)- and hemorrhage-induced acute lung injury (ALI). We also postulated that GM-CSF augments LPS-induced inflammation by priming neutrophils. ALI was induced in GM-CSF-/- or control C57BL mice either by LPS injection or by hemorrhage. Lung inflammation (by lung expression for tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin-1beta (IL-1beta), interleukin- 6 (IL-6), and keratinocyte-derived chemokine) and lung injury (by myeloperoxidase and Evans blue dye assay) were evaluated after ALI. Incremental doses of LPS (0, 1, 10, and 100 ng/mL) and GM-CSF (0, 1, 10, and 100 ng/mL) were added to bone marrow neutrophils. The expression of TNF-alpha, MIP-2, and IL-1beta was evaluated with enzyme linked immunosorbent assay. The mRNA expression of three cytokines, and the nuclear translocation of nuclear factor kappa B (NF kappa-B) were evaluated by reverse transcriptase-polymerase chain reaction and electrophoretic mobility shift assay, respectively. GM-CSF -/- mice showed decreased neutrophil infiltration, less leakage, and lower expression of cytokines in the lung after LPS or hemorrhage. GM-CSF augmented LPS-induced protein and mRNA expression of TNF-alpha, MIP-2 and IL-1beta, which was mediated by increased intra-nuclear translocation of NF-kappaB. GM-CSF plays an important role in high-dose LPS and hemorrhage-induced ALI, which appears to be mediated by its priming effect on neutrophils.
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PMID:Granulocyte macrophage-colony stimulating factor (GM-CSF) augments acute lung injury via its neutrophil priming effects. 1843 14

New data were presented at the 15th Conference on Retroviruses and Opportunistic Infections that further support the importance of considering the neuroeffectiveness of antiretroviral drugs when designing treatment regimens. Two studies linked antiretroviral therapy that had estimates of better neuroeffectiveness with better global neuropsychologic outcomes in life. A third study linked estimates of better antiretroviral therapy neuroeffectiveness, particularly nonnucleoside analogue reverse transcriptase inhibitors, with a lower prevalence of HIV-associated brain pathology at death. Additional findings presented at the conference focused on the correlates of HIV-associated neurocognitive disorders (HAND) and peripheral neuropathy. Supporting the concept that viral factors influence the pathogenesis of HAND, high frequencies of HAND were identified in people infected with HIV subtype D and in people infected with subtype B and having brain-specific mutations in V3 of gp160. Supporting the importance of host correlates of HAND, important data from a macaque study identified a strong link between a major histocompatibility complex class I allele, Mane-A*10, and simian immunodeficiency virus encephalitis. Supporting the importance of comorbidities in determining risk for HAND, high levels of lipopolysaccharide in blood, likely derived from the HIV-injured intestine and bacterial translocation, were linked to HAND. Coinfections with JC virus or Treponema pallidum were topics of other presentations, identifying a prognostic marker for PML (better CD8+ cytotoxic T-lymphocyte responses were associated with survival) and a diagnostic one for neurosyphilis (CXCL13 levels in CSF).
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PMID:Highlights of the 15th Conference on Retroviruses and Opportunistic Infections. Neurologic complications of HIV disease and their treatment. 1844 79

The advent of highly active antiretroviral therapy (HAART), which constitutes HIV protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors, has dramatically reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection in resource-rich countries. However, this disease still kills several million people each year. Though the reason for therapeutic failure is multi-factorial, an important concern is the treatment and control of HIV within the central nervous system (CNS). Due to the restricted entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site. This not only results in virological resistance, but also is often associated with the development of complications such as HIV-associated dementia. The CNS delivery of anti-HIV drugs is limited by the blood-brain and blood-CSF interfaces due to a combination of restricted paracellular movement, powerful metabolic enzymes and numerous transporters including members of the ATP binding cassette (ABC) and solute carrier (SLC) superfamilies. A better appreciation of the transporters present at the brain barriers will prove a valuable milestone in understanding the limited brain penetration of anti-HIV drugs in HIV and also aid the development of new anti-HIV drugs and drug combinations, with enhanced efficacy in the CNS. This review aims to summarise current knowledge on the transport of anti-HIV drugs across the blood-brain barrier and the choroid plexus, as well as provide recommendations for future research.
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PMID:The transport of anti-HIV drugs across blood-CNS interfaces: summary of current knowledge and recommendations for further research. 1917 19

Classical swine fever is a highly contagious, notifiable disease of pigs and wild boars listed by the World Organisation for Animal Health (OIE). Therefore, methods employed in the diagnosis of CSF should be fast, sensitive and specific. The aim of this study was optimisation of the reverse transcription reaction to increase the sensitivity of real-time RT-PCR for the detection of classical swine fever virus, the aetiological agent of the disease. The efficiency of reverse transcription reaction was compared including a range of reverse transcriptases, thermal conditions and priming methods based on results obtained in the following realtime PCR. Depending on catalysis and the priming method used in the study a significant diversity of results was observed. The best efficacy of reverse transcription was obtained using SuperScript II reverse transcriptase and priming with random nonamers and reverse, gene-specific primer. This combination improved the sensitivity of RT-PCR nearly 1000 times as compared to the method with AMV reverse transcriptase coupled with random hexamers. In summary, this study has demonstrated that the optimisation of reverse transcription can contribute to a higher sensitivity of RT-PCR diagnostic methods.
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PMID:Optimisation of reverse transcription can improve the sensitivity of RT-PCR for detection of classical swine fever virus. 2046 Feb 24

Boosted protease inhibitor (bPI) monotherapy has demonstrated high efficacy for maintaining viral suppression in the blood. bPI monotherapy has the theoretical advantage of avoiding the long-term toxicity associated with the use of nucleoside reverse transcriptase inhibitors. Concern about the efficacy of bPI monotherapy in preventing HIV replication in the CNS is one reason that has precluded the widespread use of this therapeutic strategy. In several studies, a low CNS penetration-effectiveness (CPE) score has been associated with a higher risk of virological failure in the CNS and with neurocognitive impairment. Since the CPE score is substantially lower for bPI monotherapy than for triple-drug highly active antiretroviral therapy (HAART), it has been postulated that bPI monotherapy might have a higher risk for CNS virological failure and neurocognitive impairment. However, the available evidence, although limited, does no support this notion. Lopinavir and darunavir achieve CSF drug levels that are sufficient to fully suppress HIV replication. In clinical trials, when compared with triple-drug HAART, patients receiving bPI monotherapy with lopinavir and darunavir who maintain full virological suppression in plasma do not appear to be at a higher risk of discordant HIV replication in the CSF or of neuropsychiatric adverse events. It should be noted that several studies have suggested that nucleoside reverse transcriptase inhibitors might have neurotoxic effects and, consequently, bPI monotherapy might be able to avoid the CNS toxicity induced by nucleosides. It is clear that more studies including detailed neurocognitive testing are needed to completely establish the risk/benefit ratio of bPI monotherapy or triple-drug HAART for preserving neurocognitive function in HIV-infected patients.
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PMID:Protease inhibitor monotherapy and the CNS: peace of mind? 2167 18

Bacterial infections induce exacerbations in chronic lung diseases, e.g., chronic obstructive pulmonary disease (COPD), by enhancing airway inflammation. Exacerbations are frequently associated with right heart decompensation and accelerate disease progression. Endothelin receptor antagonists (ERAs) might have therapeutic potential as pulmonary vasodilators and anti-inflammatory agents, but utility in exacerbations of chronic lung diseases is unknown. We hypothesized that cytokine releases induced by lipopolysaccharide (LPS), the major bacterial trigger of inflammation, are reduced by ERAs in pulmonary vascular smooth muscle cells (PVSMCs). Ex vivo cultivated human PVSMCs were preincubated with the endothelin-A-receptor selective inhibitor ambrisentan, with the endothelin-B-receptor selective inhibitor BQ788 [sodium (2R)-2-{[(2S)-2-({[(2R,6S)-2,6-dimethyl-1-piperidinyl]carbonyl}amino)-4,4-dimethylpentanoyl][1-(methoxycarbonyl)-d-tryptophyl]amino}hexanoate], or with the dual blocker bosentan before stimulation with smooth LPS (S-LPS), rough LPS (Re-LPS), or a mixture of long and short forms (M-LPS). Expression of cytokines and LPS receptors (TLR4, CD14) were analyzed via enzyme-linked immunosorbent assay (ELISA) and/or quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). All LPS forms induced interleukin (IL)-6-, IL-8-, and granulocyte macrophage-colony stimulating factor (GM-CSF) release. Bosentan and BQ788 inhibited M-LPS-induced release of all cytokines and soluble CD14 (sCD14) but not TLR4 expression. Ambrisentan blocked M-LPS-induced IL-6 release but not IL-8, GM-CSF, or LPS receptors. IL-8 release induced by S-LPS, which requires CD14 to activate TLR4, was blocked by bosentan and BQ788. IL-8 release induced by Re-LPS, which does not require CD14 to activate TLR4, was insensitive to both bosentan and BQ788. In conclusion, PVSMCs contribute to inflammation in bacteria-induced exacerbations of chronic lung diseases. Inhibition of the endothelin-B receptor suppresses cytokine release induced by long/smooth LPS attributable to sCD14 downregulation. ERAs, particularly when targeting the endothelin-B receptor, might have therapeutic utility in exacerbations of chronic lung diseases.
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PMID:Endothelin receptor antagonists attenuate the inflammatory response of human pulmonary vascular smooth muscle cells to bacterial endotoxin. 2372 Apr 57


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