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)

Ocular complication of AIDS are seen in about 75% of patients. Viral infections are predominant and can involve either external segment in the eye (Herpes type 8 in Kaposi sarcoma, molluscum contagiosum, Herpes simplex and zoster), or the posterior segment of the eye (CMV retinitis). The introduction of a Highly Active Antiretroviral Therapy (HAART) which associates two reverse transcriptase inhibitors and one antiprotease has changed the evolution of AIDS. The decrease of onset of CMV retinitis in AIDS patient is one of the best exemple. For the first time it was possible to stop the maintenance therapy against CMV retinitis in patients that have a sufficient increase in CD4+ cells and they did not present any relapse of CMV retinitis. But an increase of ocular inflammation can be observed with the onset of HAART such as uveitis or cystoid macular edema.
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PMID:[Diagnosis and treatment of ocular viral infections in AIDS patients]. 986 23

A two-cell system for the stimulation of herpes simplex virus type 1 (HSV-1) from an in vitro model of long-term (quiescent) infection is described. Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor were infected with HSV-1 strain 17. Little, if any, cytotoxicity was observed, and a quiescent infection was established. The long-term infection was characterized by the absence of all detectable virus in the culture medium and little, if any, detectable early or late viral-gene expression as determined by reverse transcriptase PCR analysis. The presence of HSV-1 DNA was determined by PCR analysis. This showed that approximately 180 viral genomes were present in limiting dilutions where as few as 16 cells were examined. The viral DNA was infectious, since cocultivation with human corneal fibroblasts (HCF) or human corneal epithelial cells (HCE) resulted in recovery of virus from most, if not all, clusters of PC12 cells. Following cocultivation, viral antigens appeared first on PC12 cells and then on neighboring inducing cells, as determined by immunofluorescent staining, demonstrating that de novo viral protein synthesis first occurred in the long-term-infected PC12 cells. Interestingly, the ability to induce HSV varied among the cell lines tested. For example, monkey kidney CV-1 cells and human hepatoblastoma HepG2 cells, but not mouse neuroblastoma cells or undifferentiated PC12 cells, mediated stimulation. This work thus shows that (i) quiescent HSV infections can be maintained in PC12 cells in vitro, (ii) HSV can be induced from cells which do not accumulate significant levels of latency-associated transcripts, and (iii) the activation of HSV gene expression can be induced via neighboring cells. The ability of adjacent cells to stimulate HSV gene expression in neuron-like cells represents a novel area of study. The mechanism(s) whereby HCF, HCE, and HepG2 and CV-1 cells communicate with PC12 cells and stimulate viral replication, as well as how this system compares with other in vitro models of long-term infection, is discussed.
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PMID:Human corneal cells and other fibroblasts can stimulate the appearance of herpes simplex virus from quiescently infected PC12 cells. 1019 13

We determined 3,135 bp of the nucleotide sequence located in an 8.5 kb EcoRI-E fragment in the unique long (UL) genome region of Marek's disease virus serotype 2 (MDV2), and identified UL20 and UL21 homologous genes of herpes simplex virus type 1 (HSV-1). The UL20 and UL21 homologous genes of MDV2 are arranged colinearly with the prototype sequence of HSV-1. In addition, an open reading frame (MDV2 ORF 273), which has been identified within the UL21 homologous gene of MDV2, has no apparent relation to any other known herpesvirus genes. Northern blot analysis and reverse transcriptase polymerase chain reaction confirmed the existance of RNA transcripts related to the UL20 and ORF 273 genes in MDV2-infected cells, except no transcript related to the UL21 gene being detected. The putative protein product of the MDV2 UL20 gene had a relatively low homology but that of the MDV2 UL21 gene had a moderate homology among herpesviruses. Further, the possible functions and features of the predicted proteins encoded within the sequenced region are discussed.
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PMID:Identification and DNA sequence analysis of the Marek's disease virus serotype 2 genes homologous to the herpes simplex virus type 1 UL20 and UL21. 1042 78

Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of reverse transcriptase (RT) template switching. The effect of distance between direct repeats on the rate of deletion was determined for 16 murine leukemia virus (MLV)-based vectors containing a 701-bp direct repeat of overlapping fragments of the herpes simplex virus thymidine kinase gene (HTK). The direct repeats were separated by spacer fragments of various lengths (0.1 to 3.5 kb). Southern analysis of infected cells after one replication cycle indicated that all vectors in which the distance between homologous sequences was >1,500 bp deleted at very high rates (>90%). In contrast, vectors containing <1,500 bp between homologous sequences exhibited lower frequencies of deletion (37 to 82%). To analyze the pattern of locations at which RT switched templates, restriction site markers were introduced to divide the downstream direct repeat into five regions. RT switched templates within all five regions of the 701-bp direct repeat and the frequency of template switching was greater within the 5' regions in comparison to the 3' regions. The probability of RT switching templates within the 5' regions doubled when the MLV packaging sequence (Psi) was placed between the 701-bp direct repeats. However, Psi did not increase the rate of template switching for shorter direct repeats. These results indicate that linear distance between homologous sequences increases the rate of template switching and suggest that duplex formation between nascent DNA and homologous template sequences 3' of RT promote template switching.
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PMID:Effect of distance between homologous sequences and 3' homology on the frequency of retroviral reverse transcriptase template switching. 1048 39

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in stimulating insulin release in the pancreas as well as inhibiting gastric acid secretion in the stomach. GIP has been found in specific endocrine cells located in the mucosal layer of the small intestine and in the submandibular salivary gland. In this study, the tissue-specific expression of GIP guided by 1.2 kb of the human GIP (hGIP) gene 5' flanking region was investigated by a transgenic mouse approach. A chimeric promoter-reporter gene construct linking the 5'-flanking region of the hGIP gene with the thymidine kinase gene of the herpes simplex virus was introduced into the genomes of mice by microinjection. By reverse transcriptase-PCR (RT-PCR) and thymidine kinase assays, transgene expression was found in the stomach and pancreas. The enzyme activity detected in the stomach was about 6-fold higher than that found in the pancreas, suggesting that GIP may be expressed in the stomach. This observation is supported by RT-PCR studies since both human and mouse GIP transcripts are detected in the stomach and small intestine. In addition, distinct GIP-producing cells were identified in both tissues in mouse by in situ hybridization and immunohistochemical staining. Taken together, our data demonstrate for the first time that GIP is expressed in human and mouse stomach.
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PMID:Glucose-dependent insulinotropic polypeptide gene expression in the stomach: revealed by a transgenic mouse study, in situ hybridization and immunohistochemical staining. 1050 10

Erythema multiforme follows administration of several drugs or infection with various agents, including herpes simplex virus, a syndrome designated herpes simplex virus associated erythema multiforme. Lesional skin from 21 of 26 (81%) herpes simplex virus associated erythema multiforme patients was positive for herpes simplex virus gene expression as evidenced by reverse transcriptase-polymerase chain reaction with primers for DNA polymerase and/or immunohistochemistry with DNA polymerase antibody. Reverse transcriptase-polymerase chain reaction and immunohistochemistry studies indicated that herpes simplex virus associated erythema multiforme lesional skin from 16 of 21 (76%) DNA polymerase positive herpes simplex virus associated erythema multiforme patients was also positive for interferon-gamma, a product of T cells involved in delayed-type hypersensitivity (p < 0. 0001 by Pearson correlation coefficient). Interferon-gamma signals were in infiltrating mononuclear cells and in intercellular spaces within inflammatory sites in the epidermis and at the epidermis/dermis junction. Herpes simplex virus lesional skin was also positive for DNA polymerase [five of five (100%)] and interferon-gamma [four of five (80%)], but lesional skin from drug-induced erythema multiforme patients was negative. Lesional herpes simplex virus associated erythema multiforme keratinocytes also stained with antibody to transforming growth factor-beta [14 of 23 (61%)] and cyclin-dependent kinase inhibitor waf [12 of 18 (67%)]. Staining was also seen in keratinocytes from herpes simplex virus lesions [five of five (100%)], but not in normal skin. By contrast, staining with antibody to tumor necrosis factor-alpha, another pro-inflammatory cytokine, was seen in seven of 11 (64%) drug-induced erythema multiforme patients, but not in herpes simplex virus or herpes simplex virus associated erythema multiforme patients, and lesional keratinocytes from drug-induced erythema multiforme patients were negative for transforming growth factor-beta and cyclin-dependent kinase inhibitor waf. We interpret the data to indicate that herpes simplex virus associated erythema multiforme pathology includes a delayed-type hypersensitivity component and is mechanistically distinct from drug-induced erythema multiforme.
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PMID:Herpes simplex virus associated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-gamma is expressed in HAEM lesions and tumor necrosis factor-alpha in drug-induced erythema multiforme lesions. 1057 38

Antiviral medications interfere with one or more of the six parts of the viral reproductive cycle. The five mechanisms of action of antiviral agents are used to group pharmaceuticals into categories: uncoating inhibitors, nucleic acid synthesis inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors. The pharmacokinetics and nursing implications of specific uncoating inhibitors for respiratory viruses and nucleic acid synthesis inhibitors for respiratory syncytial virus, herpes simplex, and varicella zoster viruses are described in detail.
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PMID:Common antiviral agents used in women's and children's care, part 1. 1075 Jun 84

Nitric oxide (NO) is considered an important signaling molecule implied in various different physiological processes, including nervous transmission, vascular regulation, and immune defence, as well as the pathogenesis of several diseases. NO reportedly also has an antiviral effect on several DNA and RNA virus families. The NO-mediated S-nitrosylation of viral and host (macro)molecules appears to be an intriguing general mechanism for the control of the virus life cycle. In this respect, NO is able to nitrosylate cysteine-containing enzymes (e.g., proteases, reverse transcriptase, and ribonucleotide reductase). Moreover, zinc-fingers and related domains present in enzymes (e.g., HIV-1-encoded integrase or herpes simplex virus type-1 heterotrimeric helicase-primase complex) or nucleocapsid proteins may be considered as NO targets. Also, NO may regulate both host (e.g., nuclear factor-kappaB) and viral-encoded (e.g., HIV-1 tat protein or Epstein-Barr virus Zta) transcriptional factors that are involved in virus replication. Finally, NO-mediated S-nitrosylation of cysteine-containing glycoproteins and hemagglutinin may also occur. Here, NO targets are summarised, and the molecular bases for the antiviral effect of NO are discussed.
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PMID:S-nitrosylation of viral proteins: molecular bases for antiviral effect of nitric oxide. 1079 12

This review is primarily intended for synthetic bio-organic chemists and enzymologists who are interested in new strategies in the design of virus inhibitors. It is an attempt to assess the importance of the enzymatic properties of L-nucleosides and their analogues, particularly those that are active against viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), herpes simplex virus (HSV), etc. Only data obtained with purified enzymes have been considered and discussed. The examined enzymes include nucleoside- or nucleotide-phosphorylating enzymes, catabolic enzymes, viral target enzymes and cellular polymerases. The enantioselectivities of these enzymes were determined from existing data and are significant only when a sufficient number of enantiomeric pairs of substrates could be examined. The reported data emphasize the weak enantioselectivities of cellular or viral nucleoside kinases and some viral DNA polymerases. Thus, cellular deoxycytidine kinase has a considerably relaxed enantioselectivity with respect to a large number of nucleosides or their analogues, and it occupies a strategic position in the intracellular activation of the compounds. Similarly, HIV-1 reverse transcriptase often has a relatively weak enantioselectivity and can be inhibited by the 5-triphosphates of a large series of L-nucleosides and analogues. In contrast, degradation enzymes, such as adenosine or cytidine deaminases, generally demonstrate strict enantioselectivities favouring D-enantiomers and are used by chemists in asymmetric syntheses. The weak enantioselectivities of some enzymes involved in nucleoside metabolism are more or less pronounced, and one enantiomer or the other is favoured depending on the substrate. This suggests that the low enantioselectivity is fortuitous and does not result from evolutionary pressure, since these enzymes do not create or modify asymmetric centres in substrates. The combined enantioselectivities of the enzymes examined in this review strongly suggest that the field of L-nucleosides and their analogues should be systematically explored in the search for new virus inhibitors.
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PMID:The enantioselectivity of enzymes involved in current antiviral therapy using nucleoside analogues: a new strategy? 1090 Dec 89

Acyclovir is an antiviral agent that causes termination of viral DNA synthesis by inhibiting viral reverse transcriptase. Acyclovir is used therapeutically to treat herpes simplex, cytomegalovirus, Epstein-Barr, and varicella-Zoster. Although acyclovir is thought to be low in toxicity, it has caused an obstructive nephropathy from accumulation of crystals in renal tissue. A retrospective review (January 1995 through March 2000) was conducted of acyclovir toxicoses in dogs reported to the ASPCA National Animal Poison Control Center. Of 105 ingestions, 10 were considered cases of acyclovir toxicosis. The most common signs seen were vomiting, diarrhea, anorexia, and lethargy. Ingested dosages ranged from 40 to 2195 mg/kg bw. Polyuria and polydipsia were reported in I dog. In 6/10 cases, signs developed within 3 h of ingestion. Treatment included standard decontamination procedures, (ie induction of emesis, administration of activated charcoal), diuresis, and supportive care.
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PMID:Accidental ingestion of acyclovir in dogs: 105 reports. 1111 48


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