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)

Antitumor antibiotic streptonigrin (STN-COOH) is a potent inhibitor of avian myeloblastosis virus (AMV) and human immunodeficiency virus reverse transcriptases. The carboxyl group at 2'-position of STN-COOH was modified to give esters, hydrazide, amides and amino acid derivatives for biological studies. Against AMV reverse transcriptase, the hydrazide, amides and amino acid derivatives showed inhibitory activity, which compared favorably to that of STN-COOH, with the ID50 values ranging 2-8 micrograms/ml. In contrast, the esters lacked this activity except for those having a dimethylamino group in the substituent. Splenomegaly caused by Friend leukemia virus infection was significantly inhibited by STN-COOH and STN-COO(CH2)3N(CH3)2, but not STN-CONH(CH2)3N(CH3)2. Doxorubicin-resistant murine lymphoblastoma L5178Y cells showed collateral sensitivity to both STN-COOH and STN-COO(CH2)3N(CH3)2 not only in vitro but also in vivo.
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PMID:Biological properties of streptonigrin derivatives. III. In vitro and in vivo antiviral and antitumor activities. 273 55

The effect of 3'-azido-2',3'-dideoxythymidine (AZT) on the human immunodeficiency virus (HIV)-associated giant cell formation was studied in vitro. For this purpose we developed a coculture system using Molt-4 and its virus-producing cell, Molt-4/HTLV-III, which induced syncytia very efficiently. Treatment of the cocultures with 1 and 5 microM of AZT did not inhibit induction of multinucleated giant cells, although only 0.1 microM AZT resulted in almost complete inhibition of HIV replication in Molt-4 cells by cell-free virus infection. This was also evidenced by the assays for viral antigen-positive cells, reverse transcriptase activity, and virus particles released from cell cultures after AZT treatment. When the cocultures were treated with 1% neutralizing antibody (NA) from HIV-infected individuals alone, giant cell formation was inhibited to some extent. However, the concomitant treatment of culture with AZT and NA resulted in much stronger inhibition of giant cell formation. The amount of CD4 antigens on the surface of cells was reduced greatly in the HIV producer cells (Molt-4, H9, and MT-4 cells) as compared to their HIV-free counterparts. These data suggest that (1) both CD4 antigen and viral antigens on the surface of cells play central roles in the induction of multinucleated giant cells and (2) AZT is more effective in inhibition of viral spread in patients with higher NA, probably at an earlier stage of the disease than in patients with lower NA titer.
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PMID:Effect of 3'-azido-2',3'-dideoxythymidine (AZT) and neutralizing antibody on human immunodeficiency virus (HIV)-induced cytopathic effects: implication of giant cell formation for the spread of virus in vivo. 311 Oct 83

After infection of the respective target cells with the human immunodeficiency virus (HIV-1) viral progeny is produced only after a short temporary delay of some days, depending on cell type. After this period of time a sudden onset of HIV-1 protein synthesis with a dramatic increase in virus release occurs. (2'-5')Oligoriboadenylates [(2'-5')A], capable to activate a latent ribonuclease (RNase L) degrading both mRNA and rRNA, are known mediators involved in the early response of cells to virus infection. Here we show that the (2'-5')A-synthesizing (2'-5')A synthetase, which is inducible by interferon and activated by double-stranded RNA, as well as a (2'-5')A nuclease (2',3'-exoribonuclease) are associated with the nuclear matrix of uninfected and infected H9 cells, also in the absence of interferon. Infection of H9 cells with HIV-1 was found to cause a strong (7.7-fold) enhancement of (2'-5')A synthetase activity and a smaller (2-fold) increase of 2',3'-exoribonuclease activity. Simultaneously the concentration of synthesized (2'-5')A increased 5 to 10 times in isolated nuclei. After incubation for 2 to 3 days both enzyme activities reached a maximum and then dropped below their initial values. Concomitantly a drastic increase in virus production occurred, as judged by reverse transcriptase activity in the culture fluid. These results suggest that the (nuclear matrix-associated) (2'-5')A system might be important during the initial stage of HIV infection, also by destructing matrix-bound viral messengers.
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PMID:Alteration of nuclear (2'-5')oligoriboadenylate synthetase and nuclease activities preceding replication of human immunodeficiency virus in H9 cells. 322 94

Poly(1-vinyluracil) and poly(9-vinyladenine), as well as the corresponding polynucleotides poly(uridylate) and poly(adenylate), inhibit acute murine leukemia virus infection in mouse-embryo cells, but they do not significantly inhibit the replication of Sindbis and vesicular stomatitis viruses. The polymers were most effective as inhibitors when added during an early stage of virus replication. Effects of vinyl polymers on the RNA-dependent DNA polymerase from the virions of murine leukemia virus were also observed.
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PMID:Inhibition of murine leukemia virus replication by poly(vinyluracil) and poly(vinyladenine). 412 32

Single-stranded polyribonucleotides, which competitively inhibit murine RNA tumor virus reverse transcriptase in vitro, were tested as inhibitors of various virus functions in cell culture. The compounds had two concentration-dependent effects. At high concentrations (100 mug/ml), both poly(adenylic acid) [poly(A)] and poly(2'-O-methyladenylic acid) [poly(Am)] inhibited the uptake of radioactively labeled leukemia virus by Swiss mouse embryo cells, but neither had a similar effect on Sindbis virus adsorption. At low concentrations (10 mug/ml), poly(Am) did not inhibit the uptake of leukemia virus but did inhibit virus replication by 85%; in contrast, the replication of Sendai virus and Sindbis virus was not inhibited significantly at this concentration. Both compounds were effective only when added prior to or early during virus infection. Poly(Am) was a much more effective inhibitor than poly(A), probably due to the nuclease resistance of the former compound. Poly(Am) at 5 mug/ml also inhibited transformation of 3T3 cells by Moloney sarcoma virus. However, neither poly(A) nor poly(Am) at high concentrations inhibited the activation of endogenous leukemia virus by iododeoxyuridine in AKR mouse embryo cells. These results suggest that virus reverse transcriptase plays an essential role in both the replication of exogenous murine leukemia viruses and the transformation of cells by murine sarcoma viruses but probably has no role in the activation of endogenous leukemia virus.
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PMID:Effects of polyadenylic acids on functions of murine RNA tumor viruses. 412 77

Interactions among viruses may be significant to the pathogenesis of the profound immunologic defects observed in acquired immunodeficiency syndrome (AIDS). Such interactions could include complementary immunosuppression, potentiation of infection by altered receptors or genetic complementation, phenotypic mixing, or genetic recombination. The abnormalities induced by simultaneous infection with cytomegalovirus of Epstein-Barr virus, for example, may be synergistic and suppression induced by 1 virus may permit replication of another virus to high titer. Given the alterations in cell-surface components during the course of a viral infection, it is possible that AIDS infection modifies the expression of histocompatibility antigens on lymphocyte membranes or viral receptors not normally available on a given cell become expressed during infection with a 2nd virus. An alternative, viral potentiation, occurs when 1 virus codes for a gene product required for growth of another, resulting in a greater virus yield that would be expected from either virus alone. Phenotypic mixing occurs when 2 enveloped viruses infect the same cell, and the genome of 1 becomes incorporated in an envelope composed of glycoproteins from the other. In genetic recombination, actual exchange of genetic information between viruses allows for the emergence of new viruses with altered biologic characteristics. Such recombination occurs with high frequency in the human retroviruses, probably during a phase of replication involving reverse transcriptase to viral DNA. To learn more about such interactions, viruses isolated from the blood and semen of AIDS patients should be analyzed for cell tropism, neutralization kinetics, and hybridization.
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PMID:Possible viral interactions in the acquired immunodeficiency syndrome (AIDS). 609 5

Model systems to study restricted primate retrovirus expression were established by de novo infection of canine foetal thymus cells (CF-2Th) and superinfection of HEL-12 cells with HEL-12 virus. In the resulting CF-2Th/HEL-12V cells and HEL-12/HEL-12V cells, four sequential stages of virus infection were defined by the production of reverse transcriptase (RT)-containing particles and expression of virus antigens as detected by radioimmunoassays. Stage 1 cells did not synthesize virus antigens or produce RT-containing particles. Stage 2 cells synthesized virus antigen but not RT-containing particles. Stage 3 cells synthesized antigen and produced RT-containing particles, and stage 4 cells synthesized virus antigens but no longer produced RT-containing particles. The duration of the four stage infection is 2 to 3 weeks in both cell types. Monospecific competition radioimmunoassays to detect HEL-12V p30 or gp70 antigen showed high levels of virus antigen throughout stages 2 to 4 of infection. Analysis of immunoprecipitates formed under conditions to detect either p30- or or gp70-containing proteins in cells pulsed and pulsed--chased with [3H]leucine showed the same spectrum of virus precursor polyproteins, intermediates and mature virion components in stage 2 to 4 cells in canine and human infections. Spent culture fluids collected from stage 3 and stage 4 CF-2Th/HEL-12V cells failed to reveal inhibitors of RT activity. Stage 4 CF-2Th/HEL-12V or HEL-12/HEL-12V cells labelled with [3H]uridine produced virions which incorporated [3H]uridine but did not have RT activity, suggesting that restricted infection is characterized by production of HEL-12V defective in RT activity.
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PMID:Restricted HEL-12 virus infections in de novo infected human and canine cells. 617 57

We studied a patient with a Philadelphia chromosome-positive chronic myeloid leukemia, who died in relapse after multiple transfusions and grafting with bone marrow from his monozygotic twin brother (referred to as "donor" in this paper). We present data indicating that this patient may have had a retro-virus infection that this virus is related to the group of exogenous primate type C retroviruses. Antibodies to simian sarcoma virus (SSV) M.W. 30,000 protein (p30) but not endogenous feline virus RD-114 could be found in patient but not donor serum. Patient but not donor cells were able to actively synthesize a p30 protein that could be precipitated with patient serum and rabbit anti-SSV p30 but not with donor serum or rabbit anti-RD 114 p30. Patient p30 resembles SSV p30 but not RD-114 p30 in peptide mapping by limited proteolysis and subsequent slab gel electrophoresis. Patient but not donor cells were able to actively synthesize a M.W. 78,000 protein that could be precipitated with goat anti-SSV. An enzyme with properties of reverse transcriptase was increased 30-fold ion patient cells when compared with donor and other control cells. Related to the presence of widespread infectious agents may be the finding that, in the course of the patient's disease, donor serum showed increasing amounts of possibly immunoregulatory (Cancer Research, submitted for publication) antibodies, reactive with autologous and, more effectively, with patient-derived cell membrane M. W. 80,000 protein (a possible idiotypic receptor structure) and M.W. 94,000 protein (a T-cell alloantigen).
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PMID:Synthesis of a viral protein with molecular weight of 30,000 (p30) by leukemic cells and antibodies cross-reacting with Simian sarcoma virus p30 in serum of a chronic myeloid leukemia patient. 617 17

We studied the effects of murine leukemia virus infection on the growth of tumors in inbred strain 2 guinea pigs. Fibrosarcomas, induced by treatment of guinea pig fetal cells with chemical carcinogens, were exposed in vitro to the amphotropic murine leukemia virus, 4070A. Tumor cells exposed to murine leukemia virus 4070A in vitro expressed virus antigens, released both reverse transcriptase and infectious virus into supernatant fluids, and grew and regressed after injection into syngeneic animals. In contrast, uninfected tumor cells did not express virus antigens and grew progressively. Rejection of virus-infected tumor cells appeared to be a host-mediated event, since murine leukemia virus 4070A infection had no detectable cytopathic effect on fibrosarcoma cells. Rejection of virus-infected tumor cells occurred in guinea pigs unable to suppress the growth of the line 10 hepatoma at sites of injection of mycobacterial cell walls and unable to develop immunity to the line 10 hepatoma. Guinea pigs immunized with virus-infected tumor cells were unable to reject a challenge of uninfected tumor cells. The results are interpreted to mean that infection of guinea pig tumors in vitro by a murine leukemia virus led to synthesis of viral antigens by the tumor cells which in turn led to recognition of the tumor as foreign with consequent tumor destruction; tumor eradication occurred without development of immunity to cryptic, intrinsic tumor antigens.
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PMID:Tumor rejection mediated by an amphotropic murine leukemia virus. 618 93

Tissues obtained at necropsy from a 7 year old male gibbon ape with malignant lymphoma and leukemia were analyzed by electron microscopic, immunological and enzymological techniques to determine the comparative localization of tumor cells and virus throughout the body. In general, the different assays correlated well; the reverse transcriptase (RT) assay and p30 radioimmunoassay (RIA) being the most sensitive, although the RT assay was able to detect activity in one tissue scored negative by p30 RIA. Tissues were infiltrated with tumor cells to varying degrees which correlated well with the level of virus markers in most cases with the exception of the liver and kidney. In these 2 organs there was marked infiltration of free virus and tumor cells but there was no evidence of virus infection or production by these cells.
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PMID:Comparison of the tissue distribution of reverse transcriptase, p30 and type-C virus in a gibbon ape with lymphocytic leukemia. 618 17


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