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

---

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.
...
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.
...
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

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.
...
PMID:["Pharaoh" line culture of Japanese quail cells as a leukosis-free system for virus reproduction]. 625 36

In vivo preinfection of chicks with rabies virus (RV) or vesicular stomatitis virus (VSV) ts 1026 inhibits tumour formation after superinfection with Rous sarcoma virus (RSV). The degree of inhibition depends on the titre of the infecting viruses and the interval between rhabdovirus and RSV infection. In vitro, cells preinfected with VSV ts 1026 under non-permissive conditions and superinfected with RSV, are not transformed as judged by cell morphology, serum requirement for growth or the capacity to form colonies in soft agar, all these being the same as in uninfected cells. Doubly infected cells take up less deoxyglucose than cells infected with RSV only and more than cells infected with VSV only. RSV multiplication in inhibited in doubly infected cells: the supernatant fluid of these cells contains fewer focus-forming units and less reverse transcriptase activity than that of cells infected with RSV only. Doubly infected cells contain both VSV and RSV internal antigens 15 days after infection. The supernatant fluid of cells infected with VSV and maintained under non-permissive conditions inhibits transformation by RSV and multiplication of RSV, but not of VSV. Under non-permissive conditions, the rhabdoviruses undergo at least part of the infectious cycle, but no infectious virus is produced. RV antigen can be detected in the brain of parenterally infected chicks and VSV antigen in cells infected 15 days previously. We conclude that the inhibition of RSV multiplication and expression is probably due to one or more processes linked to the persistence of rhabdovirus components and that it cannot be attributed exclusively to interferon.
...
PMID:Inhibition of Rous sarcoma virus-induced transformation by preinfection with rhabdoviruses. 630 Feb 84

Cooperation between B cells specific for an antigen exposed on a viral structure and T helper (Th) cells specific for an internal antigen, as demonstrated with influenza, hepatitis B and rabies viruses, has been termed intrastructural help. Th cells specific for internal proteins of HIV, which are much less mutated than its exposed antigens, may be valuable in vaccine design against this virus. We investigated the human Th repertoire specific for the core HIV antigen reverse transcriptase (p66), and determined whether these cells could be candidate intrastructural T helpers. CD4+ T lines and clones were generated from non-immune individuals by stimulation with p66-pulsed antigen-presenting cells (APC). Specific lines were obtained with p66 from 19 out of 21 (90%) of these individuals, vs. 7 out of 29 (24%) with gp120. Diverse epitopes were recognized by different individuals, and various V beta genes were used by these clones. Clones using the same V beta genes were of diverse origin, according to VDJ region sequence. Of these lines 45% responded to p66 in the context of HIV virions. Moreover, p66-specific clones could respond to APC that had internalized HIV complexed with envelope-specific monoclonal antibodies, suggesting that p66-specific Th cells may participate in intrastructural help. These studies indicate that p66-specific Th cells are detectable in vitro in most naive individuals and exhibit clonal heterogeneity, and that the majority recognize an HIV conserved antigen. They respond to p66 following processing of whole virions and are clearly candidates for intrastructural help. If confirmed in vivo, p66 should be included among vaccine candidates investigated to optimize the anti-HIV Th response.
...
PMID:Human T helper cells specific for HIV reverse transcriptase: possible role in intrastructural help for HIV envelope-specific antibodies. 753 50

A heminested reverse transcriptase PCR (hnRT-PCR) protocol which is rapid and sensitive for the detection of rabies virus and rabies-related viruses is described. Sixty isolates from six of the seven genotypes of rabies and rabies-related viruses were screened successfully by hnRT-PCR and Southern blot hybridization. Of the 60 isolates, 93% (56 of 60) were positive by external PCR, while all isolates were detected by heminested PCR and Southern blot hybridization. We also report on a comparison of the sensitivity of the standard fluorescent-antibody test (FAT) for rabies antigen and that of hnRT-PCR for rabies viral RNA with degraded tissue infected with a genotype 1 virus. Results indicated that FAT failed to detect viral antigen in brain tissue that was incubated at 37 degrees C for greater than 72 h, while hnRT-PCR detected viral RNA in brain tissue that was incubated at 37 degrees C for 360 h.
...
PMID:Heminested PCR assay for detection of six genotypes of rabies and rabies-related viruses. 935 Jul 29

A simple and rapid single-step reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the nucleoprotein (N) gene of 11 rabies viruses. A conserved set of RT-PCR primers was designed to amplify the most variable region in the N gene. N gene regions were amplified from 6 fixed laboratory viruses, 4 street viruses from dogs in Thailand, and a horse in Zambia. Sequences of the amplified products, together with the database of 91 additional sequences, were analyzed by using PILEUP program of the GCG package. The rabies viruses grouped into at least 9 distinct clusters by < 90% nucleotide similarity of the N gene region: I (4 isolates, USA), II (2 isolates, South America), III (3 isolates, Africa), IV (52 strains, Europe, Middle East, Africa and South America), V (16 isolates, North America and Arctic), VI (17 isolates, Africa), VII (1 isolate, Africa), VIII (6 isolates, Thailand and Malaysia) and IX (1 isolate, Sri Lanka). A unique group of rabies viruses from Thailand and clusters of isolates corresponding to their geographic origin also were determined. The simple and rapid single-step RT-PCR proved to be useful for identifying rabies viruses, and for grouping the viruses into clades by sequence analysis.
...
PMID:Nucleoprotein gene analysis of fixed and street rabies virus variants using RT-PCR. 967 37

A rapid and sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of classical rabies virus (genotype 1) and the rabies related European bat lyssaviruses (EBLs) (genotypes 5 and 6) was developed. When combined with specific oligonucleotide probes and a PCR-enzyme linked immunosorbent assay (PCR-ELISA), genotype 5 and 6 viruses can be distinguished from each other and from genotype 1 viruses. Ninety-two isolates from the six established genotypes of rabies and rabies-related viruses were screened by RT-PCR and PCR-ELISA to determine the specificity of the assays. All genotype 1, 5 and 6 viruses were detected by RT-PCR while none of the genotype 2, 3 and 4 viruses were detected. All the genotype 5 and 6 viruses were detected by the two PCR-ELISA probes when used in combination while none of the genotype 1-4 viruses were detected. When used individually, the PCR-ELISA probes also distinguished between the genotype 5 and 6 viruses. This new discriminatory test should allow the rapid genotyping of all lyssaviruses likely to be encountered in Europe and as such could provide useful epidemiological information in the event of an outbreak.
...
PMID:Molecular methods to distinguish between classical rabies and the rabies-related European bat lyssaviruses. 1085 59

Between 1981 and 1998, 37 cases of rabies were diagnosed in human beings in the United States. Information directly linking the cause of infection to animal bite was available for only eight of these cases. Indirect incrimination of the vector by analysis of cDNA sequences obtained by reverse transcriptase polymerase chain reaction of samples indicated that for all cases (12/12) believed to have been acquired in foreign countries, variants of the rabies virus (VRVs) associated with dogs (7/12 involved known bite histories) were the cause of the rabies infections. In contrast, VRVs associated with bats (bat-associated VRVs or BAVs) were implicated as the cause of 88% (22/25) of infections believed to have been acquired within the United States (1/22 involved known bite histories). Sequence analyses revealed that a single BAV (Ln/Ps), associated with rabid silver-haired (Lasionycteris noctivagans) and Eastern pipistrelle (Pipistrellus subflavus) bats, was implicated in 73% (16/22) of bat-associated infections. Silver-haired bats are predominantly solitary and migratory. Eastern pipistrelle bats may occur individually or in small clusters. Both species are only infrequently submitted for rabies testing. Unrecognized bites and unique properties of the Ln/Ps BAV may explain its association with the majority of rabies infections in human beings in the United States.
...
PMID:Mammalian reservoirs and epidemiology of rabies diagnosed in human beings in the United States, 1981-1998. 1119 44

We report a previously unrecognized complexity to the ecology of rabies in wildlife. Rabies-specific virus-neutralizing antibodies in spotted hyenas, the most numerous large carnivore in the Serengeti ecosystem (Tanzania, East Africa), revealed a high frequency of exposure of 37.0% to rabies virus, and reverse transcriptase (RT) PCR demonstrated rabies RNA in 13.0% of hyenas. Despite this high frequency, exposure neither caused symptomatic rabies nor decreased survival among members of hyena social groups monitored for 9 to 13 years. Repeated, intermittent presence of virus in saliva of 45.5% of seropositive hyenas indicated a "carrier" state. Rabies isolates from Serengeti hyenas differed significantly (8.5% sequence divergence) from those isolated from other Serengeti carnivores, suggesting that at least two separate strains circulate within the Serengeti carnivore community. This finding is consistent with the fact that exposure in hyenas increased with age and social status, following a pattern predicted by intraspecific age and social-status-dependent oral and bite contact rates. High seroprevalence of rabies, low basic reproductive rate of the virus (R(0)) of 1.9, a carrier state, and the absence of symptomatic rabies in a carnivore in an ecosystem with multihost and multistrain maintenance has not been previously demonstrated for rabies. Because of the substantial differences between the hyena viral isolates and those from canids and viverrids in the Serengeti, it is unlikely that spotted hyenas were the source of rabies virus that killed several African wild dog packs in the Serengeti ecosystem in the 1990s.
...
PMID:Regular exposure to rabies virus and lack of symptomatic disease in Serengeti spotted hyenas. 1174 89


1 2 3 4 Next >>

---