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)

Application of a highly sensitive PCR-based reverse transcriptase (RT) assay to the analysis of the infection of CD4+ cell lines with human immunodeficiency virus type 1 (HIV-1) demonstrated that virus production can be detected as early as 24 h after infection. Most of the signal at 24 h was due to virus production, as it could be substantially reduced by prior treatment with the RT inhibitor zidovudine. Virus production at 24 and 48 h was unaffected by the protease inhibitor indinavir. Infection of unstimulated peripheral blood mononuclear cells (PBMC) with a macrophage-tropic HIV-1 isolate yielded increasing virus production for 2-3 weeks, while infection with a T-cell line-tropic isolate yielded only low and sporadic virus production. Productive infection of unstimulated PBMC by the macrophage-tropic virus required functional Gag matrix and Vpr proteins; therefore, the monocyte-derived macrophage is probably the virus-producing cell in these cultures.
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PMID:Detection of human immunodeficiency virus type 1 after infection of unstimulated peripheral blood mononuclear cells. 1021 53

The aim of this study was to obtain information on the feasibility (tolerance, safety) of antiretroviral combination therapy, including ritonavir, in children. In eight children (median age 8.9 years; range 3 to 13 years) with advanced HIV disease (median CD4+ lymphocyte count at baseline, 80 cells/microliter; range 0 to 280 cells/ microliter), drug combinations including ritonavir (approximately 300 mg/m2 b.i.d.) were administered. In seven children, previous therapy using a combination of at least two nucleoside reverse transcriptase inhibitors (NRTI) had failed. Four patients had ritonavir added to an already existing regimen of two NRTI; two patients had one NRTI replaced by a new one; and in two patients two new NRTI were initiated. The number of CD4 T cells, plasma HIV RNA concentration, CBC and blood chemistry profile were monitored. Medication had to be discontinued in two children because of severe nausea and vomiting. In the remaining six children, ritonavir was tolerated and treatment was maintained for at least 6 months. The number of CD4 cells increased in five of six patients. The median number of CD4 cells increased from 66 +/- 110 cells/microliter at baseline to 92 +/- 99 cells/microliter, 161 +/- 88 cells/microliter, and 252 +/- 25 cells/microliter after 1, 3 and 6 months of therapy, respectively. The plasma HIV RNA concentration decreased below the detection limit of 500 copies/ml in three children. In the remaining children a maximum reduction of 0.8, 1.0 and 1.8 log10 was observed. In one child the HIV RNA concentration reincreased after 6 months by 0.7 log10 above the nadir. Antiretroviral combinations including ritonavir were tolerated by six of eight children and produced substantial benefits with respect to increased numbers of CD4 cells and a decline in plasma viral RNA concentration. It can be concluded that the administration of ritonavir is possible in a significant proportion of HIV-infected children, and leads to improvement of the CD4 cell count and viral load.
Infection
PMID:Preliminary experiences with ritonavir in children with advanced HIV infection. 1021 39

Feline immunodeficiency virus (FIV) was first isolated in 1987 from a cat with an acquired immunodeficiency syndrome (AIDS)-like disease. Since then, FIV has been subject of intensive research. Perturbation in cytokine production observed in human immunodeficiency virus infection (HIV) is paralleled in the FIV-infected cat. Interferon gamma (IFN-gamma) is a type 1 lymphokine that exert protective effects during infection through upregulation of cellular immunity and phagocytic functions. The present study was carried out to examine the expression of IFN-gamma in a feline T-lymphoid cell line (Fel-039) infected with FIV as well as the viral replication in these cells after addition of recombinant-type feline IFN (rIFn). We found a marked inhibition of IFN-gamma release in Fel-039 cells infected with FIV which might be pivotal for high viral replication. Infection of Fel-039 cells with FIV resulted in an increase of the reverse transcriptase (RT) activity in the culture supernatant. When the cells were cultured in the presence of rIFN a significant dose-dependent inhibition of RT activity of FIV was detected without cytotoxicity. On the basis of these in vitro results, we suggest that IFN therapies aimed at restoring depleted level of this important cytokine in FIV infected T-cells make this compound a promising candidate for development of suitable drugs for AIDS treatment.
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PMID:[Feline immunodeficiency virus infection: interferon gamma secretion in a T-lymphoblastoid infected cell line]. 1050 91

Sheep pulmonary adenomatosis (SPA), also known as jaagsiekte or ovine pulmonary carcinoma, is a contagious lung cancer of sheep, originating from type II pneumocytes and Clara cells. Previous studies have implicated a type D retrovirus (jaagsiekte sheep retrovirus [JSRV]) as the causative agent of SPA. We recently isolated a proviral clone of JSRV from an animal with a spontaneous case of SPA (JSRV(21)) and showed that it harbors an infectious and oncogenic virus. This demonstrated that JSRV is necessary and sufficient to induce SPA. A major impediment in research on JSRV has been the lack of an in vitro tissue culture system for the virus. The experiments reported here show the first successful in vitro infection with this virus, using the JSRV(21) clone. JSRV(21) virus was obtained by transiently transfecting human 293T cells with a plasmid containing the JSRV(21) provirus driven by the human cytomegalovirus immediate-early promoter. Virus produced in this manner exhibited reverse transcriptase (RT) activity that banded at 1.15 g/ml in sucrose density gradients. Infection of concentrated JSRV(21) into ovine choroid plexus (CP), testes (OAT-T3), turbinate (FLT), and intestinal carcinoma (ST6) cell lines resulted in establishment of infection as measured by PCR amplification. Evidence that this reflected genuine infection included the fact that heat inactivation of the virus eliminated it, the levels of viral DNA increased with passage of the infected cells, and the infected cells released active RT as measured by the sensitive product enhancement RT assay. The RT activity released from the infected cells banded at 1.15 g/ml, and JSRV(21) provirus was transmitted from infected cells to uninfected ones by cocultivation. However, the amount of virus released from infected cells was low. These results suggest that the JSRV receptor is present on many ovine cell types and that the observed restriction of JSRV expression in vivo to tumor cells might be controlled by factors other than the viral receptor. Finally we tagged the U3 of pJSRV(21) with the bacterial supF gene, an amber suppressor tRNA gene. The resulting clone, termed pJSRV(supF), is infectious in vitro. It may be a useful tool for future studies on viral DNA integration, since the normal sheep genome contains 15 to 20 copies of highly JSRV-related endogenous sequences that cross-react with many JSRV hybridization probes.
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PMID:In vitro infection of ovine cell lines by Jaagsiekte sheep retrovirus. 1055 21

Human immunodeficiency virus (HIV) and Kaposi's sarcoma-associated herpesvirus (KSHV) coinfect many individuals in North America and in parts of Africa. Infection with HIV is a leading risk factor for the development of Kaposi's sarcoma (KS). In this study, we tested the hypothesis that HIV infection of common or adjacent cells would stimulate replication and spread of KSHV. Infection of a primary effusion lymphoma cell line by vesicular stomatitis virus type G-pseudotyped HIV type 1 led to a rapid induction of lytic-phase KSHV replication. Induction of lytic KSHV replication by HIV required active replication of HIV. The addition of the nucleoside reverse transcriptase inhibitor azidothymidine or the protease inhibitor indinavir to the culture prevented HIV spread and inhibited the associated induction of KSHV lytic replication. Lytic replication occurred in both HIV-infected and HIV-uninfected cells within the culture, and could be induced in uninfected cells via a soluble factor released from the HIV-infected cells. Transmission of infectious KSHV to an uninfected target cell was enhanced by HIV replication and was inhibited by antiretroviral drugs. These results may have implications for the pathogenesis and treatment of KS in individuals coinfected with KSHV and HIV.
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PMID:Human immunodeficiency virus replication in a primary effusion lymphoma cell line stimulates lytic-phase replication of Kaposi's sarcoma-associated herpesvirus. 1055 51

Helper T cell cytokine and antibody responses were investigated in mice after infection with Babesia microti (King strain). Infection of CBA mice with 106 parasitized erythrocytes resulted in the development of a transitory high parasitaemia which peaked 14 days post infection (DPI), and was resolved at 24 DPI. Th1 responses were activated predominately during the acute phase (6-18 DPI) whereas Th2 responses predominated during the recovery phase (14-28 DPI) as detected by the reverse transcriptase polymerase chain reaction. Increased expression of Th1 cytokines was first detected at 6 DPI (IL-2) and 8 DPI (IFN-gamma) and their peak levels were reached at 12 DPI. After the peak levels were reached, they progressively declined and fell to baseline levels (22 DPI). Increased expression of Th2 cytokines (IL-4 and IL-10) first appeared at 14 DPI, peaked at 20 DPI and Th2 cytokine levels were elevated till the end of the study (28 DPI). Levels of serum IFN-gamma detected by a sandwich ELISA correlated well with IFN-gamma gene expression and were detectable at 8-18 DPI. IgM against B. microti was first detected in serum by ELISA at 4 DPI, and peaked at 10 DPI. The levels of IgM subsequently declined but remained positive at low titre till the end of study. IgG against B. microti was first detected at 8 DPI and peak levels were reached at 24 DPI and remained at that level until the end of study. The results of the present study show that Th1 cytokines predominated in the early inflammatory response and might be involved in control of levels of acute parasitaemia whereas the Th2-associated responses, including expression of IL-4 and IL-10 and the production of parasite-specific IgG, might be the functional means for the reduction and clearance of the parasite from the body. It was concluded that an effective vaccine against Babesia spp. should be designed to induce Th1 responses to maintain the parasitaemia at unfulminating levels and also maintain Th2 responses to clear the parasite from the body.
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PMID:Helper T cell and antibody responses to infection of CBA mice with Babesia microti. 1065 20

Anti-HIV drug regimens can fail for a number of reasons including virological resistance, difficulties of adherence and poor tolerability. However, this brief review focuses on the development of "pharmacological" resistance as an area of great importance in drug failure. For nucleoside reverse transcriptase inhibitors (NRTIs) this is related to the possible down-regulation of the intracellular phosphorylation of an NRTI with time. For protease inhibitors the concern is cells expressing transmembrane energy-dependent transporters (such as p-glycoprotein, p-gp; or multi-drug resistance protein, MRP) which efflux drug (particularly protease inhibitors) out of the cell so that intracellular concentrations of drug are insufficient for antiviral effect.
Infection 1999
PMID:Pharmacological issues relating to viral resistance. 1088 28

Several first-generation nucleoside analogues have been tested against chronic hepatitis B virus (HBV) infection, but trials were unsuccessful or accompanied by toxicity. Recently, oral second-generation nucleoside analogues have been developed that have potent activity against HBV. The best-studied compound so far is lamivudine ((-)2'-deoxy-3'-thiacytidine; 3TC). Lamivudine is an inhibitor of reverse transcriptase (RT) activity and is in clinical use in human immunodeficiency virus (HIV)-infected individuals. As several studies on the use of lamivudine for hepatitis B show, the development of resistance in the viral polymerase under lamivudine treatment, however, causes a significant clinical problem. All other drugs in advanced clinical development for HBV are nucleosides; cross-resistance is therefore expected in most cases. The history of HIV treatment demonstrates that new classes of drugs, the protease inhibitors and non-nucleosidic inhibitors of RT, allowed for a longer-term clinical benefit when used in combination with nucleoside analogues. The development of non-nucleosidic compounds with different modes of action therefore appears very important for the treatment of chronic hepatitis B as well.
Infection 1999
PMID:Development of resistance and perspectives for future therapies against hepatitis B infections: lessons to be learned from HIV. 1088 29

Infection of peripheral blood mononuclear cells (PBMNCs) has been demonstrated to be a crucial event in the vertical transmission of viruses, and it is known that hepatitis C virus (HCV) can infect PBMNCs. The relationship between vertical transmission of HCV and the presence of positive and negative strands of HCV-RNA in the PBMNCs of HCV-carrier mothers was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR). During the study, 13 consecutive mothers who transmitted infection to their offspring and 53 consecutive mothers who did not were examined. The positive strand of HCV-RNA was identified in the PBMNCs of all mothers who transmitted the infection and in 13 of 53 mothers who did not (P < 10(-6)). The HCV-RNA(-) strand was found in 5 of 13 mothers who transmitted the infection, and the strand was not found in the mothers who did not transmit the infection (P =.0001). Neither maternal PBMNC infection nor HCV transmission to the offspring was significantly related to the viral genotype or to the maternal viral load. These data show that maternal PBMNC infection by HCV and viral replicative activity in PBMNCs are important factors in the transmission of HCV from mother to child. The mechanism through which HCV infection of PBMNC favors vertical transmission of the virus is still incompletely understood.
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PMID:Vertical transmission of HCV is related to maternal peripheral blood mononuclear cell infection. 1097 45

Infection of mouse trigeminal ganglia by herpes simplex virus induces cytokine expression that persists long after infectious virus or viral antigens become undetectable. To examine mechanisms underlying this phenomenon, we used a thymidine kinase mutant, dlsptk, which fails to replicate in ganglia and does not reactivate upon ganglionic explant. Using quantitative reverse transcriptase-polymerase chain reaction assays, we found that levels of interferon-gamma and tumor necrosis factor-alpha transcripts in dlsptk-infected ganglia were lower than those in wild type-infected ganglia, but were significantly (eight- to 10-fold) higher than those in mock-infected ganglia from Day 3 to Day 100 postinfection. We also studied latency-associated transcript (LAT) negative mutants that exhibit increased expression of productive cycle transcripts in ganglia. Ganglia infected with these mutants contained levels of cytokine transcripts similar to those in wild type-infected ganglia; any increases in viral antigen expression mediated by the LAT deletion were not accompanied by increased cytokine expression. Thus, neither viral replication, the ability to reactivate, nor LAT expression in ganglia is required for persistent elevated cytokine expression. The results provide indirect evidence that low-level expression of viral productive cycle genes in neurons can provide signals that elicit cytokine expression.
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PMID:Persistent elevated expression of cytokine transcripts in ganglia latently infected with herpes simplex virus in the absence of ganglionic replication or reactivation. 1111 95


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