Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
Disease
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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)
Phylogenetic trees of two different retroviral gene products were constructed by using the progressive alignment method. The
reverse transcriptase
domain and the amino-terminal region of the transmembrane
env protein
, including the fusagenic peptide domain of at least one member of each of the established retrovirus subfamilies or groups, were separately aligned. The resulting phylogenetic tree of the
reverse transcriptase
was compared to that of the transmembrane protein. The similarities and differences are discussed with respect to the genetic events that occurred during the evolution of retroviruses. A segment of the central part of the viral
env protein
sequence was found to have 22% to 37% homology with some members of the immunoglobulin superfamily.
...
PMID:Comparative analysis of the retroviral pol and env protein sequences reveal different evolutionary trees. 169 51
Human T cell lymphotropic virus type I (HTLV-I) gag and
env protein
-specific antibodies were identified in 6 of 13 patients with essential cryoglobulinemia (EC), by Western blot and radioimmunoprecipitation analysis. Supernatants of cells from 2 of the 5 EC patients tested showed
reverse transcriptase
activity. DNA sequences homologous to HTLV-I could not be detected by polymerase chain reaction, thus excluding the presence of prototype HTLV-I in each patient with EC. The data suggest that retroviral proteins distinct from but related to HTLV-I may be involved in the pathogenesis of EC in some patients.
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PMID:Antibodies to retroviral proteins and reverse transcriptase activity in patients with essential cryoglobulinemia. 171 86
A total of 81 cell clones persistently infected with the LAV-1 or HTLV-IIIB strain of human immunodeficiency virus type 1 (HIV-1) was isolated from cells which were obtained by serial passage of some proliferating MT-4 cells after a drastic cytolysis of most cells by HIV-1-infection. These cell clones were classified into 8 types (I to VIII) in terms of the expression of HIV-1 antigens, syncytium formation capacity, and
reverse transcriptase
activity and infectivity of virus particles in the culture fluid. Type I cell clones were producers of infectious HIV-1 particles, while types II to VIII cell clones did not produce infectious HIV-1 or were producers of uninfectious defective HIV-1 particles. Immunoprecipitation followed by SDS-polyacrylamide gel electrophoresis (PAGE) showed that the gag precursor protein in L-2 cell clone (type IV) was not cleaved to mature gag proteins, while the env precursor protein on L-3 cell clone (type III) was not cleaved to mature
env protein
. H-7 cell clone (type VIII) did not express any HIV-1 antigen. All these cell clones after the superinfection with infectious HIV-1 synthesized intact gag and env proteins, which were, at least in part, related to the HIV-1 genome persistently present in the cell clones before the superinfection, resulting in production of infectious HIV-1. For example, it was found that L-2 cell clone contained a single copy of the LAV-1 genome per haploid cell and produced doughnut-shaped particles. On the other hand, the cell clone isolated from the L-2 cell clone superinfected with infectious HTLV-IIIB contained the integrated HTLV-IIIB genome in addition to the LAV-1 genome present before the superinfection, and produced intact HIV-1 particles in addition to doughnut-shaped particles from a single cell. These results indicate that complementation and/or genetic recombination events in the superinfected cells may account for the production of infectious intact HIV-1 virions.
...
PMID:Production of infectious particles from defective human immunodeficiency virus type 1 (HIV-1)-producing cell clones by superinfection with infectious HIV-1. 200 Nov 75
Three pig-tailed macaques were vaccinated twice, four weeks apart, with a human T-cell lymphotropic virus type 1 (HTLV-1) subunit vaccine. Four weeks post-vaccination, the vaccinated macaques and two control monkeys were challenged with a simian T-cell lymphotropic virus type 1 (STLV-1)-infected cell line. Following the first vaccination, an antibody response developed to HTLV-1 and STLV-1 viral proteins as visualized by Western blot. The antibody recognized both gag and
env protein
precursors and the titer remained elevated after the second vaccination. After challenge, the antibody titers of the vaccinates increased. The controls also developed HTLV-1 and STLV-1 specific antibody which recognized the gag precursor and to a lesser extent the putative tax protein. Immunized monkeys also produced syncytium inhibiting antibody primarily toward HTLV-1-infected cells and to a lesser extent toward STLV-1-infected cells. Control monkeys produced negligible amounts of syncytium inhibiting antibody. Additionally, both polymorphonuclear (PMN) and mononuclear (MNC) cells were examined. The PMN population was tested for its ability to generate an oxidative burst. Neither vaccination nor challenge had any significant effect on the PMN CL response. The MNCs were tested for their capability to proliferate after stimulation. Again, no significant change occurred. However, when examined for cell-mediated cytotoxicity, the MNCs from immunized monkeys produced greater cytotoxic activity against the HTLV-1-infected cell line than the MNCs from control monkeys. In order to determine if the immunized monkeys were protected by the subunit vaccine against the STLV-1 challenge,
reverse transcriptase
(RT) activity was measured in the five monkey's MNCs. RT activity was exclusively present in the non-immunized, control monkeys implying that the HTLV-1 subunit vaccine was successful in protecting the pig-tailed macaques from the STLV-1 infection.
...
PMID:Efficacy of an HTLV-1 subunit vaccine in prevention of a STLV-1 infection in pig-tailed macaques. 217 25
We have shown that 6D5 cells infected with the HIV-1 strain HTLV-III451 (6D5(451)) secreted viral envelope proteins gp160 and gp120 into the culture medium. Single cell cloning of 6D5(451) cells separated three distinct phenotypes. All clones secreted unprocessed
env protein
gp160 along with gp120. Only one phenotype produced infectious virus and contained normally processed gag proteins. The second phenotype was associated with nonproducer cells expressing only the env gene but no extracellular particles. The third phenotype synthesized Pr53gag but no
reverse transcriptase
, nor did it process the gag precursor. Only immature particles could be seen in the culture. Cells of the first and the third phenotypes produced two sizes of gp160, the normal and one with a small truncation at the C-terminus. Phenotype 2 only produced the smaller gp160. In all cases the gp160 that was secreted into the medium was the truncated molecule.
...
PMID:Differential viral gene expression and its effect on the biological properties of the cell clones of an HIV-1-infected cell line. 235 62
An amphotropic retrovirus packaging cell line was constructed in which the gag, pol, and env genes of the helper virus are separated on two different plasmids and in which the packaging signals and 3' long terminal repeats are removed. To do this, a plasmid containing the Moloney murine leukemia virus gag and pol gene was transfected into NIH 3T3 cells, and a plasmid containing the 4070A amphotropic env gene was transfected into one of the resulting clones which produced a high level of
reverse transcriptase
. A clone producing a high level of amphotropic
env protein
(GP + envAm12) was then isolated. When transfected into GP + envAm12 cells, titers of the retroviral vector N2, containing a neomycin resistance gene, ranged from 10(2) to greater than 10(6) CFU/ml on 3T3 cells, from 1.3 x 10(4) to 2.7 x 10(5) CFU/ml on HeLa cells, and from 1.0 x 10(2) to 6.0 x 10(3) CFU/ml on K562 cells when assayed by G418 resistance. These titers were comparable to titers obtained using the PA317 cell line. Tests for the safety of the GP + envAm12 packaging line showed no evidence for the generation of wild-type virus. Thus, the efficiency and safety of the GP + envAm12 cell line in gene transfer into human cells may provide an optimal system for experiments whose goal is human gene therapy.
...
PMID:Construction and use of a safe and efficient amphotropic packaging cell line. 246 7
A retrovirus packaging cell line was constructed by using portions of the Moloney murine leukemia virus in which the gag, pol, and env genes of the helper virus were separated onto two different plasmids and in which the psi packaging signal and 3' long terminal repeat were removed. The plasmid containing the gag and pol genes and the plasmid containing the env gene were cotransfected into NIH 3T3 cells. Clones that produced high levels of
reverse transcriptase
and
env protein
were tested for their ability to package the replication-defective retrovirus vectors delta neo and N2. One of the gag-pol and env clones (GP+E-86) was able to transfer G418 resistance to recipient cells at a titer of as high as 1.7 X 10(5) when it was used to package delta neo and as high as 4 X 10(6) when it was used to package N2. Supernatants of clones transfected with the intact parent gag-pol-env plasmid 3P0 had comparable titers (as high as 6.5 X 10(4) with delta neo; as high as 1.7 X 10(5) with N2). Tests for recombination events that might result in intact retrovirus showed no evidence for the generation of replication-competent virus. These results suggest that gag, pol, and env, when present on different plasmids, may provide an efficient and safe packaging line for use in retroviral gene transfer.
...
PMID:A safe packaging line for gene transfer: separating viral genes on two different plasmids. 283 75
The analysis of retroviral mutants has played a critical role in the development of our understanding of the complex viral life cycle. The most fundamental result of that analysis has been the definition of the replication functions encoded by the viruses. From a biochemical examination of a particular step in the life cycle it is difficult to determine, for example, whether that step is catalyzed by a viral or a host enzyme; but the isolation of a viral mutant defective in that step can firmly establish that a viral function is involved. In this way many facts about the viruses have been established. We know that
reverse transcriptase
is encoded by the virus; that RNAase H and DNA polymerase activities reside on the same gene product; that processing of many precursor proteins is mediated by a viral proteinase; and that establishment of the integrated provirus requires a viral protein. The list of functions mediated by viral enzymes has largely been defined by the mutants isolated and studied in various laboratories. The second significant result of the studies of viral mutants has been the assignation of the replication functions to particular viral genes, and then more specifically to particular domains of these genes. Mutants and viral variants have been essential in the determination, for example, that the gag protein is the critical gene product for the assembly of a virion particle; that the
env protein
is the determinant of species specificity of infection; or that the LTR is a major determinant of tissue tropism and leukemogenicity. The subdivisions of functions within a given gene have similarly hinged on mutants. Genetic mapping was needed to establish that P30 is the most important region for assembly; that the proteinase and integrase functions reside, respectively, in the 5' and 3' portions of the pol gene; and that the glycosylated gag protein is dispensable for replication. A third important area of knowledge has depended heavily on viral mutants: the determination of host functions and proteins that interact with viral proteins. Variant viruses with altered or restricted host ranges serve to define differences between pairs of different host cells, and the mapping of the viral mutations serves to define the viral protein important in that interaction with the host. These studies are only in their infancy, but it is clear that substantial efforts will be made to further analyze these host functions.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Mutants of murine leukemia viruses and retroviral replication. 303 30
Synchronized mouse cells (JLS-V9) chronically infected with Rauscher murine leukemia virus were used to study virus production, the synthesis of gag and env precursor proteins, and the expression of
env protein
on the cell surface during the cell cycle. The amount of virus released into the medium by synchronized cells during a 30-min interval was determined by using the XC plaque assay and by measuring
reverse transcriptase
activity. The results show that virus production occurs during mitosis. Labeling of the cell surface of synchronized cells with 125I or with fluorescein-conjugated antiserum shows that the amount of gp 70env on the cell surface parallels cellular growth. Therefore, the cell cycle-dependent release of virus is not accompanied by similar variations in the amount of viral envelope protein on the cell surface. Immunoprecipitation of cells labeled with [35S]methionine, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was used to measure viral protein synthesis during the cell cycle. The rate of synthesis of gag precursor proteins show three maximums corresponding to the G1, middle S, and late S to G2 phases of the cell cycle. The rate of synthesis of env precursor proteins does not change, suggesting that in these cells the synthesis of these two gene products is controlled separately.
...
PMID:Retrovirus gene expression during the cell cycle. I. Virus production, synthesis, and expression of viral proteins in Rauscher murine leukemia virus-infected mouse cells. 728 18
Sarcoidosis is a granulomatous disorder of unknown etiology. Accumulated data suggest that one or several exogenous or altered self antigens participate in producing pathophysiological change in sarcoidosis. Recently, analysis of retroviruses such as HTLV-1 and HIV-1 revealed that these viruses would produce autoimmune disease like symptoms including interstitial lung disease like pulmonary manifestation. We hypothesized novel type retrovirus or retrovirus related antigens might be a putative pathogen for sarcoidosis. Syncytial cell formation or cytopathic effect was observed in 6 of 24 patients (25%) after coculture of sarcoid BALF cells with U937 cells. Five of 18 culture supernatant showed moderate
reverse transcriptase
activity. Expression of clone 4-1
env protein
, one of the endogenous retroviral elements, was also observed in alveolar macrophages of sarcoidosis. These data encourages the further investigation of retrovirus as the pathogen of sarcoidosis.
...
PMID:[Retroviral infection as a putative pathogen for sarcoidosis]. 804 31
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