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)

Poly(I).poly(C12U) or interferon treatment inhibited multiplication of the xenotropic baboon type C endogenous retrovirus M7 in chronically infected human AV3-M7 cells, as determined by a reverse transcriptase (RT) assay and electron microscopy. Furthermore, this polynucleotide induced 2'5' oligoadenylate (2'5'A) synthetase activity. In contrast to interferon (IFN), poly(I).poly(C12U) did not give rise to the appearance of a trapping phenomenon observable by electron microscopy. When AV3-M7 cells were treated simultaneously with poly(I).poly(C12U) and anti-IFN-beta/alpha antibodies, the induction of 2'5'A synthetase was abolished without any alteration of the inhibitory effect of RT activity. Taken together, these results suggest that different mechanisms are used by poly(I).poly(C12U) and IFN in blocking type C retrovirus multiplication.
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PMID:The effects of poly(I).poly(C12U) and interferon on the multiplication of a mammalian type C retrovirus in human cells. 138 6

Interferon-alpha is an effective treatment for a subset of patients with AIDS-associated Kaposi's sarcoma. When given at high doses to patients who lack systemic signs, symptoms, and opportunistic infections associated with advanced HIV infection and who maintain some degree of cell-mediated immune function, tumor regression may be observed in a high proportion of patients. Although the addition of chemotherapy to IFN-alpha appears to confer no added benefits, the combination of IFN-alpha with zidovudine has induced high tumor response rates in preliminary studies, including responses in some patients considered unlikely to respond to IFN-alpha alone. IFN-alpha-induced tumor regression has also been associated with suppression of HIV, as measured by serum p24 antigen concentrations and peripheral blood virus cultures. Other biologic agents, including interferons beta and gamma, tumor necrosis factor, and IL-2, have also been tested, to a lesser extent, in patients with Kaposi's sarcoma. Although systemically administered IFN-beta and intralesional TNF injections have led to tumor regression in some cases, the role of these biologics has been incompletely defined. Additional studies of these agents in combination with nucleoside reverse transcriptase inhibitors such as zidovudine will be required to fully assess their role in the treatment of Kaposi's sarcoma and HIV infection. It can also be anticipated that newer biologic agents, which specifically inhibit the production or action of angiogenic factors believed to be involved in the genesis of Kaposi's sarcoma, will be studied in the near future.
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PMID:Interferon and other biologic agents for the treatment of Kaposi's sarcoma. 170 60

Monocytes treated with interferon-alpha (IFN-alpha) at virus challenge show no evidence of human immunodeficiency virus (HIV) infection: no p24 antigen or reverse transcriptase (RT) activity, no viral mRNA and no proviral DNA. Levels of p24 antigen and RT activity in monocytes infected with HIV 1-3 weeks before IFN-alpha treatment gradually decrease to baseline. HIV-induced cytopathic changes are markedly reduced, as are levels of HIV mRNA: the frequency of productively infected cells is less than or equal to 1%. But, levels of proviral DNA in the IFN-alpha-treated and control HIV-infected cells are indistinguishable, and remain so through 3 weeks. Large quantities of proviral DNA in IFN-alpha-treated cells with little active transcription suggest true microbiological latency. The major potential source for IFN-alpha in HIV-infected patients is the macrophage. With any of 15 virus isolates, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, IFN-omega or IFN-beta are not detected nor the mRNA expressed in HIV-infected or uninfected monocytes. Both uninfected and HIV-infected monocytes produce high levels of these cytokines after treatment with synthetic double-stranded RNA (poly-I:C). Uninfected monocytes also produce high levels of IFN-alpha after treatment with Poly-I:C, Newcastle disease virus or herpes simplex virus. In marked contrast, HIV-infected monocytes express no IFN-alpha activity or mRNA before or after treatment with any of these agents. The markedly diminished capacity of HIV-infected monocyte to produce IFN-alpha reflects a specific transcriptional block and may be an adaptive mechanism of virus to alter basic microbicidal functions of this cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of cytokine and viral gene expression in monocytes infected with the human immunodeficiency virus. 188 15

In a survey of 15 different virus isolates, no IFN-alpha or IFN-beta activity was detected in culture fluids of HIV-infected T cells or monocytes. Exogenous rIFN-alpha added to T lymphoblast or monocyte cultures induced restriction in replication of the amphotropic HIV that infect both cell types. With IFN-treated HIV-infected T cells, levels of reverse transcriptase (RT) activity in culture fluids were half those in control cultures, but the frequency of infected cells or the levels of p24 Ag released in culture fluids were unchanged. In contrast to the modest effect of IFN on HIV-infected T cells, IFN-induced antiviral activity in monocytes was quite dramatic. Monocytes treated with IFN at the time of virus challenge showed no evidence of HIV infection: no p24 Ag or RT activity, no viral mRNA, and no proviral DNA. In this system, IFN interrupts one or more early event(s) in the virus replication cycle before formation of proviral DNA. Monocyte cultures infected with HIV 7 days before IFN treatment showed a gradual decrease in levels of p24 Ag and RT activity to baseline by 3 wk. HIV-induced cytopathic changes were markedly reduced, and the frequency of productively infected cells was less than or equal to 1% of total cells. Virus particles released 24 h after IFN treatment were 100- to 1000-fold less infectious than equal numbers of control virions. But, monocytes treated with IFN 7 days after HIV infection were not free of the retroviral pathogen: levels of proviral DNA in the IFN-treated and control HIV-infected cells were indistinguishable. The presence of large quantities of proviral DNA in cells with little or no evidence for active transcription documents a situation approaching true microbiological latency.
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PMID:Regulation of HIV replication in infected monocytes by IFN-alpha. Mechanisms for viral restriction. 197 1

The effect of human interferons (IFNs) (alpha, beta, and gamma) on the in vitro replication of AIDS viruses (LAV, HTLV-III, and ARV-2) in human peripheral blood lymphocytes was investigated. At the time of peak virus production, IFN-alpha preparations (leukocyte, Namalwa, alpha 1, and alpha 2) at 100 U/ml, suppressed LAV, HTLV-III, and ARV-2 replication as measured by reverse transcriptase (RT) activity by greater than 50%. This suppression was dose dependent and high dosages (500 U/ml) of IFN-alpha resulted in almost complete suppression of RT activities (77-99%). A low dose (100 U/ml) of IFN-beta suppressed all three AIDS viruses by 75%. In contrast, human IFN-gamma at a dose range from 100 U/ml to 500 U/ml had no significant effect on the production of infectious viruses. These results indicate that only IFN-alpha and -beta are effective against LAV, HTLV-III, and ARV-2 replication. A continuous supply of IFN appeared to be essential for the constant suppression of RT activity. In fact, upon termination of single IFN treatment, enhanced virus production resulted.
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PMID:Human alpha- and beta-interferon but not gamma- suppress the in vitro replication of LAV, HTLV-III, and ARV-2. 242 14

Rauscher murine leukemia virus (R-MuLV) induces a rapidly developing erythroleukemia in BALB/c mice. Previously, we have shown that mouse interferon-alpha/beta (Mu IFN-alpha/beta) applied shortly after virus inoculation efficiently inhibits the leukemic process (Hekman et al., 1981). Here we describe the effect of Mu IFN-alpha/beta on an established leukemia. Varying doses of Mu IFN-alpha/beta were injected over 3 days, starting 8 to 12 days after virus inoculation. The effect of Mu IFN-alpha/beta on the leukemic process was monitored by measuring the spleen weight, reverse transcriptase activity in the serum and, in selected experiments, by microscopic examination of sections of the spleen using standard histological and immunological staining techniques. Depending on the spleen weight at the start of its application (maximal about 450 mg), Mu IFN-alpha/beta caused a dramatic reduction in the number of virus-infected erythroleukemic cells in the spleen. Also, R-MuLV disappeared from the serum within 3 days. If Mu IFN-alpha/beta was injected into R-MuLV-infected mice with an already 10-fold enlarged spleen, it could only stop further development of leukemia. Results obtained with crude Mu IFN-alpha/beta preparations were confirmed with absolutely pure Mu IFN-beta.
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PMID:The effect of murine interferon-alpha/beta on an established Rauscher murine leukemia virus-induced erythroleukemia in BALB/c mice. 258 Aug 3

The biological response modifier r(I)n.r(C12-U)n, referred to here as mismatched double-stranded (ds) RNA, was examined for antihuman immunodeficiency virus (HIV) activity in vitro because of its known antiviral activity and ability to induce interferon (IFN) in other biological systems [Carter, W. A., Strayer, D. R., Hubbell, H. R. & Brodsky, I. (1985) J. Biol. Response Modif. 4, 495-502]. We found that cultures of the highly HIV-permissive T-cell line C3 were afforded significant protection from HIV infection when incubated in growth media supplemented with mismatched dsRNA at 10-50 micrograms/ml prior to virus challenge. Similar results were obtained at 50 micrograms of mismatched dsRNA per ml in cultures of the T-lymphoblastoid cell line CEM. Infections were monitored by indirect immunofluorescence of cells for viral p24 antigen expression, reverse transcriptase activity in culture fluids for virus production, and vital dye uptake for cytopathic effect. Antiviral activity was increased by the continued presence of mismatched dsRNA in cultures following virus challenge. A one-time exposure to mismatched dsRNA (50 micrograms/ml) provided greater antiviral activity than either a one-time exposure to recombinant IFN-alpha [250 international units (IU)/ml], IFN-beta (250 IU/ml), or IFN-gamma (50 IU/ml) in cultures of CEM cells, or a one-time exposure to a combination of all three IFNs (150 IU each per ml) in cultures of C3 cells. Mismatched dsRNA at 50 micrograms/ml had no effect on cell division, RNA and protein synthesis, or virus replication in all T-cell lines examined. A clear distinction between the activities of mismatched dsRNA and IFN was the ability of IFN to suppress the in vitro replication of HIV that occurred at IFN concentrations (150 IU each of alpha, beta, and gamma per ml) that provided less antiviral activity than mismatched dsRNA (50 micrograms/ml). The results of these in vitro studies suggest a potential therapeutic value for mismatched dsRNA in the treatment of acquired immunodeficiency syndrome (AIDS).
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PMID:Antiviral activity of mismatched double-stranded RNA against human immunodeficiency virus in vitro. 310 82

The expression of the cytokine genes was studied under physiological conditions in normal adult mice using RT-PCR method capable of detecting low levels of mRNA. Total RNA was prepared from brain, spinal cord, lung, spleen, liver and kidney of 6 to 8 week-old specific pathogen-free BALB/c mice by acid guanidinium thiocyanate-phenol-chloroform (AGPC) method. cDNA was synthesized by M-MLV reverse transcriptase, and amplified using the specific oligonucleotide primers for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, IFN-beta and IFN-gamma by PCR method. Although IL-1 mRNA was detected in all the organs, IL-3 mRNA was not detected in any organs tested. IL-2 or IL-4 mRNA and IL-5 mRNA were produced only in spleen and lung, respectively. However, IL-6, TNF-alpha and IFN mRNA were detected in some different organs. These results suggest that many kinds of cytokine mRNA were produced in vivo under physiological conditions in normal mice.
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PMID:[Expression of cytokine messenger RNA in mice in physiological conditions]. 751 36

The induction of the cytokine mRNA after infection with Herpes simplex virus (HSV) was studied using RT-PCR method capable of detecting low levels of mRNA. Total RNA was prepared from spleen lymphocytes 3 h after infection with HSV-1 (+GC virulent variant and -GCr attenuated variant of Miyama strain) by acid guanidinium thiocyanate-phenol-chloroform (AGPC) method. cDNA was synthesized by M-MLV reverse transcriptase, and amplified using the specific oligonucleotide primers for IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alpha, IFN-alpha, IFN-beta and IFN-gamma by PCR method. After HSV-1 infection, IFN-alpha, IFN-beta, IFN-gamma, IL-1 beta, IL-4, IL-6 and TNF-alpha mRNA were significantly induced, but IL-2, IL-3 and IL-5 mRNA were not induced. Although IFN-alpha, IFN-gamma and IL-6 mRNA were more strongly induced by infection with +GC virulent variant than -GCr attenuated variant, there was no significant difference in the expression of other cytokine mRNA between two variants. These results demonstrate that cytokine mRNA in addition to IFN was induced by HSV infection, and suggest that cytokines as well as IFNs may play a role in the defense mechanism against HSV infection.
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PMID:[Induction of messenger RNA of cytokines by Herpes simplex virus infection in mice]. 751 38

The outer surface lipoproteins of Borrelia burgdorferi, OspA and OspB, stimulate the production of nitric oxide (NO) by murine bone marrow-derived macrophages from BALB/c, C3H/HeN, and C3H/HeJ mice. Gamma interferon (IFN-gamma) caused a three- to fivefold enhancement of this production of NO, and the L-arginine analog N-guanidino-monomethyl L-arginine inhibited it. Activation of transcription of the inducible NO synthase gene in stimulated macrophages was demonstrated by reverse transcriptase rapid PCR. Although IFN-gamma increased the amount of NO produced in macrophage cultures, it did not cause transcription of the inducible NO synthase gene greater than that seen with the Borrelia proteins. OspA and OspB also induced the production of high levels (40 to 150 ng/ml) of IFN-gamma in cultures of macrophages incubated with interleukin-2 (IL-2)-elicited cells from normal (T and NK cells) and scid (NK cells) mice but not in macrophages or IL-2-elicited cells cultured individually. This suggests that OspA stimulated macrophage production of cytokines, which, in turn, stimulated the production of IFN-gamma by NK and T cells. Reverse transcriptase rapid PCR demonstrated that OspA and sonicated B. burgdorferi stimulated production of several inflammatory cytokines in macrophage cultures, including IL-1, IL-6, IL-12, IFN-beta, and tumor necrosis factor alpha. As tumor necrosis factor alpha, IFN-beta, and IL-12 are potent activators of IFN-gamma production by T and NK cells, their presence in these cocultures could be responsible for the IFN-gamma production. Lymphocytes from infected C3H mice also produced IFN-gamma when stimulated with B. burgdorferi; thus, immune cells may also modulate NO responses. The generation of NO during infection with B. burgdorferi may be important, as NO has potent antimicrobial properties. NO can also be involved in pathological inflammatory processes in which its generation is detrimental to the host. Thus, the colocalization of B. burgdorferi lipoproteins, NO-producing cells, and regulatory cytokines may determine the outcome of infection.
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PMID:Outer surface lipoproteins of Borrelia burgdorferi stimulate nitric oxide production by the cytokine-inducible pathway. 752 Apr 17


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