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)

Our recent efforts have been directed at the development of selective inhibitors of different classes of viruses, including adeno, pox, and herpesviruses [herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV)], (+/-)RNA viruses (reo- and rotavirus), (-)RNA viruses (influenza, parainfluenza, measles, respiratory syncytial, vesicular stomatitis and rabies virus) and retroviruses [i.e. human immunodeficiency virus (HIV), the causative agent of AIDS]. In this search, the following molecular targets were envisaged: for DNA viruses in general, the viral DNA polymerase; for herpes simplex virus and varicella-zoster virus, the viral DNA polymerase via a specific phosphorylation by the viral 2'-deoxythymidine (dThd) kinase; for (+/-)RNA and (-)RNA viruses, S-adenosylhomocysteine (SAH) hydrolase, a key enzyme in transmethylation reactions required for the maturation of viral mRNA; for retroviruses, reverse transcriptase as initiator of virus replication and/or cell transformation; and for several enveloped viruses (i.e. retro-, herpes- and rhabdoviruses), virus adsorption to the outer cell membrane. Several new compounds have been developed that appear to act at these targets: i.e. (E)-5-(2-bromovinyl)-2'-deoxyuridine [bromovinyldeoxyuridine (BVDU)] and derivatives thereof [i.e. carbocyclic BVDU (C-BVDU)] as well as derivatives of acyclovir (i.e. 8-substituted acyclovir derivatives) as inhibitors of herpesviruses; (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and other phosphonylmethoxyalkylpurines and -pyrimidines as inhibitors of DNA viruses and retroviruses; acyclic and carbocyclic analogues of adenosine [such as (S)-9-(2,3-dihydroxypropyl)adenine [S)-DHPA), carbocyclic 3-deazaadenosine (C-c3Ado), (RS)-3-adenin-9-yl-2-hydroxypropanoic acid (AHPA) alkyl esters, neplanocin A, 3-deazaneplanocin A and the 5'-nor derivatives of neplanocin A and 3-deazaneplanocin A] as inhibitors of (+/-)RNA and (-)RNA viruses; 2',3'-dideoxynucleoside analogues as inhibitors of retroviruses; and sulfated polysaccharides (i.e. heparin, dextran sulfate, pentosan polysulfate, mannan sulfate), sulfated polyvinylalcohol and co-polymers of sulfated polyvinylalcohol with acrylic acid as inhibitors of retro-, herpes- and rhabdoviruses.
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PMID:Selective virus inhibitors. 169 49

We compared an antigen capture assay (Abbott Laboratories, North Chicago, Ill.) with a reverse transcriptase assay to identify and quantify human immunodeficiency virus (HIV) in culture. In direct comparisons of serial dilutions of lymphadenopathy-associated virus type 1, the antigen assay was 100-fold more sensitive than the reverse transcriptase assay in detecting the virus. The antigen assay reacted strongly with 60 different HIV isolates but did not cross-react with human T-cell lymphotropic virus type I, human T-cell lymphotropic virus type II, cytomegalovirus, varicella-zoster virus, herpes simplex virus type 1, Epstein-Barr virus, adenovirus type 5, or poliovirus type 1 or with extracts from four different control human cell lines and eight different phytohemagglutinin-stimulated normal human lymphocytes. Peripheral blood lymphocyte samples from 50 individuals were evaluated by both the antigen assay and the reverse transcriptase assay. The cells from the 34 seropositive individuals were all positive by the antigen assay (range, 3 to 9 days; average time, 5.9 days) and the reverse transcriptase assay (range, 7 to 16 days; average time, 9.6 days). Cells from the 16 seronegative individuals were negative by both assays. These results indicate that the antigen assay is an important addition to the monitoring of HIV production in the lymphocytes of infected patients.
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PMID:Comparison of antigen assay and reverse transcriptase assay for detecting human immunodeficiency virus in culture. 244 34

We have previously described model systems for cytokine-induced regulation of chronically HIV-infected promonocyte and T cell clones. Using these systems, we have shown that monokines contained in supernatants from LPS-stimulated human monocyte/macrophages (MO) up-regulate HIV expression, reflected by an increase in reverse transcriptase activity, viral RNA levels, and expressed viral proteins. Current studies were designed to determine whether viral Ag can interact with MO and secondarily affect HIV1 expression by stimulating monokine production. We found that certain herpes-group viruses, including CMV and EBV, augment HIV1 expression by inducing monokine production, whereas others, such as HSV1, HSV2, varicella-zoster virus, and human herpes virus 6 were unable to function in this capacity. The HSV1 and HSV2 Ag which failed to stimulate monokine production did not interfere with MO stimulation by CMV Ag, suggesting that failure to induce HIV expression was not attributable to MO suppression. When nonherpes group viruses were tested, we found that human adenovirus, hepatitis B virus, and vaccinia virus all failed to stimulate the production of monokines capable of activating HIV in the chronically infected cell lines. In contrast, HIV1 can augment its own expression by inducing the secretion of monokines which up-regulate HIV expression in the infected cells. The viral Ag-induced MO supernatants capable of up-regulating HIV expression did so in a dose-dependent manner, whereas viral Ag alone produced no significant change. Monokine production mediated by viral Ag was not attributable to contaminating endotoxin. These studies provide a model to determine whether other opportunistic infections may induce the expression of HIV by indirect mechanisms, such as the stimulation of cytokine production.
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PMID:Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. 254 45

Reverse transcriptase-linked PCR was used to determine the prevalence of varicella-zoster virus (VZV) gene 21 transcription in latently infected human ganglia. Under conditions wherein reverse transcriptase-linked PCR detected > or = 1,000 transcripts, VZV gene 21 RNA, but not VZV gene 40 RNA, was found in ganglia but not other tissues from five of seven humans.
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PMID:Varicella-zoster virus (VZV) transcription during latency in human ganglia: prevalence of VZV gene 21 transcripts in latently infected human ganglia. 788 21

Amplification of viral nucleic acids from the cerebrospinal fluid (CSF) has considerably improved the diagnosis of several acute, subacute and chronic viral infections of the nervous system. In herpes simplex virus (HSV) encephalitis (HSE) the polymerase chain reaction (PCR) has become the method of choice for the rapid, non invasive diagnosis. Other herpes virus associated diseases which can now be reliably diagnosed are encephalitis, ventriculoencephalitis, polymyeloradiculitis, myelitis and an inflammatory polyradiculoneuropathy caused by cytomegalovirus (CMV), HSV, varicella-zoster virus (VZV) or Epstein-Barr virus (EBV), EBV associated primary B-cell-lymphoma of the brain, acute aseptic meningitis in young adults allied with VZV, and meningoencephalitis with recurrent seizures due to human herpes virus type 6 (HHV-6). In AIDS patients, PCR has helped to differentiate lesions either due to the human immunodeficiency virus (HIV) itself or to opportunistic infections such as progressive multifocal leukoencephalopathy (PML) caused by JC virus (JCV) or CMV related complications. HIV can be detected early in the course of infection in the CSF and the amount of proviral DNA in CSF cells seems to be correlated with the severity and/or progression of neurological signs and symptoms. Acute epidemic aseptic meningitis caused by enterovirus infections can now be reliably diagnosed and typed by reverse transcriptase PCR (RT-PCR). Meningitis cases caused by vaccination with the Jeryl Lynn and Urabe vaccine strain of mumps virus have been identified using RT-PCR and sequencing of the amplified products (amplicon).
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PMID:Clinical implications of nucleic acid amplification methods for the diagnosis of viral infections of the nervous system. 879 10

For many years, acyclovir has been used to treat herpes simplex and varicella zoster infections in adults and children, although new drugs with improved bioavailability and dosage regimens (ie, famciclovir, valaciclovir) are replacing it for the outpatient management of these conditions in adults. Acyclovir remains the treatment of choice for severe herpes infections in both immunocompetent and immunosuppressed patients. Data on the newer antiherpes drugs in children are not available. Treatment of severe cytomegalovirus infections with ganciclovir and foscarnet is difficult because of toxicity; whether improved formulations of these drugs or newer agents prove clinically useful remains to be seen. For the most part, treatment of other herpesviruses is not indicated. The major advance in pediatric HIV treatment is the reduction in vertical transmission with peripartum zidovudine, although the optimal use of antiretrovirals in this situation remains to be determined. The nucleoside analogues zidovudine, zalcitabine, didanosine, and stavudine have been assessed in HIV-infected children; pediatric data about appropriate combinations (eg, with the protease inhibitors and the nonnucleoside reverse transcriptase inhibitors) and dosage regimens lag well behind the adult literature. The effectiveness of ribavirin in respiratory syncytial virus disease is uncertain. Preliminary data suggest that interferons may have a role in the management of chronic hepatitis B and C.
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PMID:Advances in antiviral therapy. 908 51

This article describes several approaches to a selective therapy of virus infections: (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU [brivudin]) for the therapy of herpes simplex virus type 1 and varicella-zoster virus infections: (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC [cidofovir]) for the therapy of various DNA virus (i.e., herpesvirus, adenovirus, papillomavirus, polyomavirus, and poxvirus) infections; 9-(2-phosphonylmethoxyethyl)adenine (PMEA [adefovir]) for the therapy of retrovirus, hepadnavirus, and herpesvirus infections; (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for the therapy and prophylaxis of retrovirus and hepadnavirus infections; and nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(IH)-one and -thione (TIBO), 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), alpha-anilinophenylacetamide (alpha-APA), and 2',5'bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxat hiole- 2",2"-dioxide)pyrimidine (TSAO) derivatives, and thiocarboxanilides for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. For the clinical use of NNRTIs, some guidelines have been elaborated, such as starting treatment with combinations of different compounds at sufficiently high concentrations to effect a pronounced and sustained suppression of the virus. Despite the diversity of the compounds described here and the different viruses at which they are targeted, they have a number of characteristics in common. As they interact with specific viral proteins, the compounds achieve a selective inhibition of the replication of the virus, which, in turn, should be able to develop resistance to the compounds. However, as has been established for the NNRTIs, the problem of viral resistance may be overcome if the compounds are used from the start at sufficiently high doses, which could be reduced if different compounds are combined. For HIV infections, drug treatment regimens should be aimed at reducing the viral load to such an extent that the risk for progression to AIDS will be minimized, if not avoided entirely. This may result in a real "cure" of the disease but not necessarily of the virus infection, and in this sense, HIV disease may be reduced to a dormant infection, reminiscent of the latent herpesvirus infections. Should virus replication resume after a certain time, the armamentarium of effective anti-HIV and anti-herpesvirus compounds now available, if applied at the appropriate dosage regimens, should make the virus return to its dormant state before it has any chance to damage the host. It is unlikely that this strategy would eradicate the virus and thus "cure" the viral infection, but it definitely qualifies as a cure of the disease.
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PMID:In search of a selective antiviral chemotherapy. 933 68

Laboratory techniques for the diagnosis of central nervous system (CNS) infections are rapidly improving but at present have limitations that necessitate our guarded enthusiasm. Enteroviruses are the most common infectious agents of viral meningitis for which an etiology can be determined, and it is anticipated that the use of the reverse transcriptase polymerase chain reaction (RT-PCR) technique should significantly improve the identification of the etiologic agent of aseptic meningitis. The combination of the polymerase chain reaction technique with laboratory methods for the determination of intrathecal antibody production to herpes simplex virus and varicella-zoster virus have improved the rapidity with which these viral infections can be diagnosed. The pearls and pitfalls of the use of these laboratory techniques in the diagnosis of viral meningitis, recurrent meningitis, and focal encephalitis are included. Recommendations for the empiric therapy of bacterial meningitis in children and adults have changed because of the emergence of penicillin and cephalosporin-resistant pneumococcal organisms. The currently recommended antibiotics and their dosages are included. The evidence for the efficacy of dexamethasone therapy in bacterial meningitis is provided. Meningitis due to Mycobacterium tuberculosis is increasingly recognized, and the initiation of empiric antituberculous chemotherapy should not await the results of CSF cultures. Toxoplasma encephalitis and primary CNS lymphoma are the most common cause of mass lesions in patients with HIV, and the diagnostic techniques to distinguish between these two infections is reviewed. A short discussion of the best test for the diagnosis of neurosyphilis is provided.
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PMID:Pearls and pitfalls in the diagnosis and management of central nervous system infectious diseases. 960 16

Simian varicella virus (SVV) infection of non-human primates is used as a model to study the pathogenesis and latency of varicella-zoster virus (VZV), the etiological agent of chickenpox and shingles. Uracil DNA glycosylase (UDG) is a DNA repair enzyme responsible for excision of uracil residues misincorporated into DNA. UDG is conserved throughout the herpesvirus family and may play an important role in viral pathogenesis. This study identified a 300 amino acid SVV UDG that shares 53.9% amino acid identity with the VZV UDG. The SVV UDG is expressed in infected Vero cells as determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis. The SVV UDG is encoded on a 2.0 kb transcript which also appears to encode the SVV glycoprotein L (gL) and the VZV gene 58 homolog. The SVV UDG is enzymatically active as determined by the ability of a SVV UDG-maltose binding protein fusion construct to remove [(3)H]-uracil incorporated into DNA.
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PMID:Identification and characterization of the simian varicella virus uracil DNA glycosylase. 1060 70

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


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