Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On theoretical grounds we propose that the essential step in the development of subacute sclerosing panencephalitis (SSPE) after measles virus infection involves a reverse transcriptase-mediated change to a DNA form, probably brought about by co-infection with a leukovirus at a critical point in time. We further suggest that this new DNA then replicates either as the core of a new slow virus or as a membrane-attached viroid exhibiting a form of non-structural integration with host cell DNA resembling that found with the herpes viruses.
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PMID:The relationship between measles virus infection and subacute sclerosing panencephalitis (SSPE). 93 14

We describe a technique, called reverse transcriptase (RT) in situ PCR, whereby RNA may be nonisotopically detected in fixed cells when amplified by PCR after cDNA synthesis by RT. RT in situ PCR using primers specific for the measles virus generated an intense signal in most measles-infected HeLa cells, as compared to the weak signal generated in few cells using standard in situ hybridization analysis. The viral RNA that localized to the nucleus spared the nucleoli, was most evident when the RT step used the primer complementary to the negative genomic strand, and was demonstrated in all multinucleated cells and the majority of uninucleate cells. A hybridization signal was evident with standard RNA in situ hybridization using the human megakaryocyte cell line Dami and a probe for glycoprotein IIB (GIIB) mRNA but not a probe for amyloid precursor protein (APP) or gelsolin (GEL) mRNA. After RT in situ PCR, signals were evident for each target localizing to the nucleolus for APP and to perinucleolar and cytoplasmic locations for GEL and GIIB. The latter findings suggest that mRNAs may follow different geographic pathways as they progress from premessage to transcriptionally active message.
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PMID:In situ localization of PCR-amplified human and viral cDNAs. 128 36

Paget's disease of bone is a disease of unknown etiology. The demonstration of viral-like particles on ultrastructural examination and the putative detection of viral antibodies and nucleic acids in the tissues suggest a possible viral association. The purpose of this study was to search for nucleic acid sequences homologous to measles virus using the recently described reverse transcriptase (RT) polymerase chain reaction (PCR) in situ hybridization (ISH) technique. After performing RT PCR ISH utilizing primers specific for the nucleocapsid region of the measles virus, an intense signal was evident in most measles-infected HeLa cells compared with a weak signal in few of these cells using standard cDNA-RNA ISH analysis. Amplified measles nucleic acid was detected in tissue from a patient who died of measles infection and was not detected in any of the 11 cases of Paget's disease of bone studied or in a giant cell tumor of bone that had tubuloreticular inclusions on electron microscopy. Therefore, these data suggest that infection by the measles virus is not associated with Paget's disease of bone.
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PMID:In situ analysis of Paget's disease of bone for measles-specific PCR-amplified cDNA. 134 74

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 have determined the nucleotide sequence of the L gene of vesicular stomatitis virus (VSV), New Jersey serotype (Ogden strain) by primer extension dideoxy sequencing of the genomic RNA with reverse transcriptase. This analysis completes the entire genomic sequence of the VSVNJ (Ogden). Comparison of the deduced amino acid sequence of this L protein with those reported for L proteins of Indiana serotype and Hazelhurst strain of New Jersey serotype revealed an extensive sequence similarity among all three proteins. The comparison was further extended to the L proteins of other nonsegmented negative-strand RNA viruses, namely the rabies virus and four members of the paramyxovirus family: measles, Newcastle disease, human parainfluenza 3, and Sendai viruses. Our findings confirmed the existence of conserved as well as unique domains in the L proteins, suggesting an evolutionary relationship among these viruses.
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PMID:Nucleotide sequence analysis of the L gene of vesicular stomatitis virus (New Jersey serotype): identification of conserved domains in L proteins of nonsegmented negative-strand RNA viruses. 215 16

A monoclonal antibody-based enzyme immunoassay (EIA) has been developed for detection of human T-cell lymphotropic virus type I (HTLV-I) core protein. The monoclonal antibody (clone 6.11) specifically recognizes the p19 gag gene-encoded protein of the virus. The EIA was over 100 times more sensitive than reverse transcriptase measurement and was capable of responding to less than 500 pg of whole-virus lysate. The assay exhibited type specificity in that HTLV-II antigens failed to produce a positive signal. In addition, a panel of other viruses demonstrated no antigenic cross-reactivity. These included herpesviruses, measles virus, human immunodeficiency viruses, and others. Viral p19 was followed during the course of density gradient ultracentrifugation in the presence of detergent, where it was noted to associate with viral membrane proteins. In comparison, reverse transcriptase activity localized in fractions of higher density containing envelope-free cores. Of clinical interest, the EIA was used to detect HTLV-I antigen in the viral cultures of patients with HTLV-I-associated myelopathies and from symptom-free individuals with proviral integration.
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PMID:Immunodetection of human T-cell lymphotropic virus type I core protein in biological samples by using a monoclonal antibody immunoassay. 219 Oct 15

A cross-sectional study of 128 individuals infected with human immunodeficiency virus type 1 (HIV-1) was conducted to determine the correlation of reverse transcriptase-inhibiting (RTI) antibody to clinical disease. Thirty-two individuals were studied in each of four clinical groups: asymptomatic individuals, those with persistent generalized lymphadenopathy, those with acquired immune deficiency syndrome (AIDS)-related complex, and those with AIDS. Our study showed that 78% of asymptomatic individuals, 53% of those with persistent generalized lymphadenopathy, 50% of those with AIDS-related complex, and only 25% of those with AIDS have RTI antibody. Concurrent measurement of measles antibody level was used as an indicator of the immune status of these individuals. Measles antibody did not decline in persons with clinical disease, but asymptomatic individuals had lower antibody titers, possibly due to hypergammaglobulinemia associated with advanced HIV infection. These results indicate that more HIV-infected asymptomatic individuals than symptomatic individuals have RTI antibody. This suggests either that the RTI antibody level decreases with the progression of disease in HIV infection or that symptomatic individuals do not produce RTI antibody. The presence or absence of RTI antibody can thus be used as a marker of advanced disease.
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PMID:Cross-sectional study of reverse transcriptase-inhibiting antibody as a marker of acquired immune deficiency syndrome. 247 22

Contamination of Japanese quail, strain Pharaoh, cell culture with oncogenous and infectious avian viruses was studied. The susceptibility of the embryonal cell cultures of the Japanese quail, strain Pharaoh, to measles, parotitis and fixed rabies viruses was also determined. It was found that the sera of pubertal quails had no antibody to Rous sarcoma virus (RSV), strains Brian, RSV (RAV-1), Schmidt-Ruppin, Carr-Zilber, as well as to Marek's disease and Newcastle disease viruses. No reverse transcriptase activity was detected in the embryonal alantoic fluid of this avian species. The quails were less susceptible, as compared to the chicken, to Schmidt-Ruppin and Carr-Zilber strains of RSV. Measles, parotitis and fixed rabies viruses reproduced actively in the Japanese quail, Pharaoh strain, embryonal cell cultures. It is suggested that the embryonal cell cultures of this avian species can be used as a leukemia-free substrate for experimental studies and manufacturing of viral vaccines.
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PMID:["Pharaoh" line culture of Japanese quail cells as a leukosis-free system for virus reproduction]. 625 36

Analysis of urine specimens by using reverse transcriptase-PCR was evaluated as a rapid assay to identify individuals infected with measles virus. For the study, daily urine samples were obtained from either 15-month-old children or young adults following measles immunization. Overall, measles virus RNA was detected in 10 of 12 children during the 2-week sampling period. In some cases, measles virus RNA was detected as early as 1 day or as late as 14 days after vaccination. Measles virus RNA was also detected in the urine samples from all four of the young adults between 1 and 13 days after vaccination. This assay will enable continued studies of the shedding and transmission of measles virus and, it is hoped, will provide a rapid means to identify measles infection, especially in mild or asymptomatic cases.
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PMID:Detection of measles virus RNA in urine specimens from vaccine recipients. 749 55

Papaverine hydrochloride (PAP) has previously been shown to have a potent inhibitory effect on the replication of viruses such as cytomegalovirus (CMV) and measles. In this report the effect of PAP on human immunodeficiency virus (HIV) replication and T lymphocyte cell function were examined. MT4 cells infected with HIV strain 3b were incubated with serial dilutions of PAP (1-30 microM). At selected times postinfection HIV replication was measured by reverse transcriptase activity (RT) or HIV p24 Ag. PAP significantly inhibited HIV replication by more than 99% at doses of 30 microM with an CD50 and ED50 of 32 microM and 5.8 microM respectively. The mechanism of inhibition of HIV caused by PAP appeared independent form its ability to increase intracellular levels of cAMP and was not mediated via a direct effect on RT activity. To examine T cell function, peripheral blood mononuclear cells (PBMC) from normal donors were stimulated with phytohemagglutinin (PHA) or CMV Ag in the presence or absence of PAP (1-30 microM). At selected times proliferative response to PHA and CMV Ag were determined by [3H]thymidine uptake. In addition, interferon (IFN) gamma and interleukin 2 (IL2) response to mitogens were measured by radioimmunoassay (RIA). PAP enhanced PHA induced IFN production at doses of 1-10 microM and CMV Ag induced IFN production at doses of 1-3 microM. Higher doses were inhibitory. PAP did not affect IL-2 production or IL2 receptor expression and had an inhibitory effect on mitogenic responses.
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PMID:Papaverine hydrochloride: effects on HIV replication and T-lymphocyte cell function. 750 1


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