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)

The role of cell-surface proteoglycans in human immunodeficiency virus (HIV) infection of T-cell lines was investigated. HIV-1-susceptible lymphoblastic T-cell lines, MT-4 and H9, were analyzed for proteoglycan synthesis and found to make heparan sulfate (HS) and chondroitin sulfate proteoglycans. Enzymatic treatment of these cells with heparitinase, but not chondroitinase, significantly prevented HIV-1(IIIB) infection as measured by inhibition of cytopathicity, reverse transcriptase production, and syncytia formation. Sulfation of glycosaminoglycans HS chains was critical to viral entry as shown by inhibition of viral infection with sodium chlorate and its specific reversal with exogenous sulfate addition. Quantitation of direct virus binding to cells showed that treatment of cells with heparitinase inhibited HIV-1 binding to the T-cell surface. Exogenous HS added to cultures inhibited virus infection in a manner analogous to dextran sulfate, further supporting a functional role for HS in HIV-1 binding. These results provide evidence for participation of cell-surface HS proteoglycans in HIV-cell attachment and virus entry.
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PMID:Cell-surface heparan sulfate proteoglycan mediates HIV-1 infection of T-cell lines. 809 45

The first accepted report of a novel human, slow virus disease belonging to "lentivirus" known as acquired immunodeficiency syndrome can be traced to reports of June 1981. HIV-1 and HIV-2 were later found over the period 1984-86 to be unequivocally associated with AIDS. They are two serologically distinct viruses belonging to the same family with the unique properties of integration and latency in the host cell genome and the presence of reverse transcriptase. Typical of all retroviruses, the HIV genome comprises three genes governing the synthesis of all core proteins, replication protein encoding, and envelope proteins. HIV uses the CD4 antigen on T-helper cells, and about 40% of blood monocytes and tissue macrophages as a cell surface receptor. HIV may, however, also infect cells which contain no CD4. Macrophages serve as the main reservoir of HIV and may carry the virus to different organs. Very recently a rare type of white blood cell called the dendritic cell has been found to allow for direct infection by HIV during sexual intercourse. These cells are prominently present in the anal and vaginal mucosa. The authors discuss facts and figures on the HIV epidemic, the Indian scenario, classification of the clinical spectrum, the enzyme immunoassay HIV testing format, Western blot, immunofluorescence antibody, HIV culture, flow cytometry, radio immuno precipitation assay, and the detection of HIV DNA. Significant advances have been made over the last ten years in understanding the pathogenesis of HIV infection and accurately diagnosing infected individuals, with recombinant technology, polymerase chain reaction, and the construction of synthetic hybrid virus rapidly becoming part of routine diagnostics. More sensitive, specific, and rapid techniques are, however, needed for the early diagnosis and management of AIDS cases. The need for more ideal antibody incorporating both regulatory and structural proteins of the virion, preferably manufactured using recombinant or peptide synthesis technique, with high purity and concentrations must be viewed seriously.
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PMID:Science challenging HIV infection. 827 85

Sindbis virus (SV) causes an acute encephalomyelitis in mice. A T cell-dependent inflammatory response is first detected 3 days after infection and includes T cells, B cells, and macrophages. The cytokines produced locally by intrinsic cells of the brain in response to infection and by infiltrating mononuclear cells and their contributions to outcome of infection have not been identified. Semiquantitative reverse transcriptase-PCR was used to evaluate the expression of mRNAs for IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, leukemia inhibitory factor (LIF), and TGF-beta in the brain during fatal and nonfatal SV encephalitis of immunocompetent BALB/cJ and immunodeficient scid/CB17 mice. IL-1 beta and IL-6 mRNAs were detected in uninfected mice before infection and were up-regulated within 24 h. TGF-beta mRNA was also constitutively expressed in uninfected mice. LIF mRNA was occasionally detected in uninfected mice but increased in amounts only in BALB/cJ not scid mice after infection. TNF-alpha, IL-4, and IL-10 mRNAs were not found in uninfected mice but were induced within 24 h and continued to rise through 7 days after infection with substantially higher levels in BALB/cJ than scid mice. These data suggest that intrinsic brain cells produce IL-1, IL-4, IL-6, IL-10, LIF, and TGF-beta mRNAs in response to viral infection. IFN-gamma and IL-2 mRNAs were detected only in BALB/cJ mice and not until 3 days after infection with the initiation of inflammation. IL-4 and IL-10 mRNAs were more persistent and more easily detectable than IL-2 and IFN-gamma mRNAs. These data suggest a predominant type 2 cytokine response in the brain during SV encephalitis. BALB/cJ mice infected with a neurovirulent strain of SV (NSV), had 100% mortality, whereas NSV-infected scid mice developed persistent nonfatal infection. Inflammation was more intense in NSV-infected mice, however, no substantial differences in cytokine mRNA levels were detected when compared with mice with nonfatal SV infection suggesting that the cytokines measured do not in and of themselves lead to fatal central nervous system disease.
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PMID:Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus encephalitis suggests a predominant type 2 T cell response. 830 Nov 32

The hepatitis B virus is a member of an unusual family of noncytopathogenic, hepatotropic DNA viruses--the hepadnaviruses. The complete virus comprises a lipoprotein coat, the hepatitis B surface antigen, enveloping a nucleocapsid core that contains a small, circular DNA molecule. Four open reading frames have been identified on the hepatitis B virus DNA genome. They encode seven proteins, including a hepatitis B virus DNA polymerase molecule with reverse transcriptase activity. The replication of the virus resembles that of retroviruses and occurs predominantly but not exclusively in hepatocytes. Virus variants involving genomic mutations have been identified. Testing for hepatitis B surface antigen permits detection of many but not all acutely infected patients. Diagnosis of acute infection rests on the identification of IgM antibodies to the hepatitis B core antigen. Antibody to hepatitis B surface antigen appears in serum during the convalescent phase of hepatitis B virus infection. It is the neutralizing, protective antibody largely responsible for immunity to reinfection. In persistent infection hepatitis B surface antigen is present, antibody to hepatitis B core antigen is predominantly an IgG antibody, antibody to hepatitis B surface antigen is not detectable or is present in very low titers and viral replication may be active. Persistent infection leads to an asymptomatic carrier state, chronic hepatitis, cirrhosis and hepatocellular carcinoma. No specific treatment exists for acute hepatitis B virus infection. Current data indicate that approximately 50% of adults who have chronic infection achieve virologic, biochemical and histologic remission from treatment with alpha-2b-interferon.
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PMID:Hepatitis B today: clinical and diagnostic overview. 832 12

Antibody to hepatitis C as measured by the ELISA method is common in alcoholics. The presence of antibody to C 100-3 has been associated with more advanced disease. However, few studies have investigated the clinical significance of hepatitis C infection as defined by the presence of circulating viral RNA in alcoholics. We have prospectively examined 48 consecutive alcoholic patients for the presence of antibody to hepatitis C by an ELISA for antibody to the C100-3 antigen and by the reverse transcriptase polymerase chain reaction (PCR) using nested primers for the 5' nontranslated region of the viral RNA. Patients with liver disease were scored for disease severity by the combined clinical and laboratory index (CCLI). Overall, 12 of 48 patients (25%) were ELISA positive and eight of 48 (16%) were PCR positive. Among the 34 patients with liver disease, 10 (29%) were ELISA positive and six (18%) were PCR positive. All PCR-positive patients were also ELISA positive. There was no significant difference in the disease severity score (CCLI) or the duration of clinical disease in PCR-positive versus PCR-negative patients with liver disease. However, PCR-positive patients were significantly younger (43 +/- 6 vs. 55 +/- 10 yr, p = 0.001), indicating an earlier onset of severe disease in PCR-positive patients. There were no false-negative ELISA tests in either those with or those without liver disease. Among the 34 patients with liver disease, four of 10 patients with positive antibody were negative by PCR. Neither individual immunoglobulin levels (IgG, IgM, IgA) nor total globulins were significantly different between the ELISA-positive/PCR-negative patients and ELISA-positive/PCR-positive patients. When the entire group of 34 patients with liver disease was considered, we could not detect a significant correlation between ELISA absorbance and total globulins, and only a weak correlation between absorbance and immunoglobulin G (p = 0.49). These data show that the majority of alcoholic patients with liver disease and positive antibody to hepatitis C also have demonstrable viremia by PCR, and may require further evaluation and treatment. Elevated immunoglobulins in these patients do not correlate strongly with ELISA absorbance for anti-HCV. The presence of clinically advanced disease at a significantly younger age in the PCR-positive group is consistent with the concept of synergy between active viral infection and alcohol abuse in the development of liver disease in alcoholic patients.
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PMID:Hepatitis C infection by polymerase chain reaction in alcoholics: false-positive ELISA results and the influence of infection on a clinical prognostic score. 831 32

We have used an efficient cDNA subtraction library procedure to identify newly induced genes in human B lymphocytes infected for 6 h with Epstein-Barr virus (EBV). Among the genes identified by automated sequencing of a random subset of clones from this library, one coded the EBV BCRF1 open reading frame, which specifies the viral interleukin 10 gene (vIL-10). This molecule is highly homologous to human (h)IL-10 and was previously thought to represent a "late" viral gene expressed only during the lytic phase of virus replication. Using gene amplification by reverse transcriptase polymerase chain reaction of B cell RNA obtained at varying times after infection, we detected vIL-10 expression within a few hours of EBV infection, followed, 20-30 h later by expression of hIL-10. Expression of both genes continued beyond the initial transformation phase (5-10 d) and was present in all transformed cell lines tested. When added at the time of viral infection, antisense (but not sense) oligonucleotides for vIL-10 mRNA (cytosolic half-life, approximately 6 h) prevented subsequent B cell transformation. The antisense effect was highly specific, leaving the expression levels of other transformation-related genes intact. Addition of exogenous (h)IL-10 rescued the transformation process in antisense-treated cells. Our observations establish vIL-10 as a new latency gene with a directly transformation-prerequisite function.
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PMID:Viral interleukin 10 is critical for the induction of B cell growth transformation by Epstein-Barr virus. 839 76

Immune suppression has long been recognized to be a consequence of measles and a likely contributor to the secondary complications of this infection. Since measles virus can be isolated from peripheral blood leukocytes during the early phases of infection, it has been widely assumed that measles virus suppresses the immune system by replicating in and damaging T lymphocytes. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay able to detect wild-type strains of measles virus was applied to the study of peripheral blood mononuclear cells (PBMC) during natural measles virus infection. Measles virus RNA was detected by RT-PCR in monocyte-enriched adherent cells up to 6 days after the appearance of the rash. No viral RNA was detected in the lymphocyte-enriched nonadherent cell fraction. The numbers of virus-infected PBMC detected by in situ hybridization ranged from 1 in 125 to 1 in 2500. Dual staining identified infected cells as monocytes. It is concluded that the primary leukocytes infected during measles are monocytes, not lymphocytes. This cellular tropism has implications for understanding the immune suppression associated with measles.
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PMID:Infection of monocytes during measles. 851 32

The prevalence and the characteristics of hepatitis C virus infection (HCV) in 161 HIV-positive patients were studied. HCV seroprevalence was determined by enzyme immunoassay and recombinant immunoblot assay (RIBA). Two different reverse transcriptase polymerase chain reaction (RT-PCR) methods were also used to test the HCV-seropositive samples and 50 EIA-negative sera used as controls. The RNA HCV-positive sera were genotyped by the LiPA procedure. Associations of HCV status with demographic characteristics and risk factors were assessed by chi 2 and Fisher's exact tests. The seroprevalence of HCV was 34.2% with a significant difference between blood and sexual exposure risk groups (60.6% vs. 13.6%, respectively; P < 0.0001). Thirty-six of the 55 anti-HCV-positive sera were also positive for HCV RNA, and PCR detected HCV RNA in 8 HCV-seronegative patients. Various RIBA profiles were found and all sera were positive for antibodies to the c33 protein. A proportion of sera had elevated levels of transaminase activity (37.2%), and abnormal liver function as associated with HCV infection. Forty-two samples were genotyped and five genotypes and subtypes of the HCV virus were detected. Genotype 1a was the most frequent in this cohort, although genotype 1b is generally more common in France. The majority (94.1%) of the patients with genotype 1a had a history of blood exposure, which may account for the difference.
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PMID:Hepatitis C virus infection in an HIV-positive population in Normandy: antibodies, HCV RNA and genotype prevalence. 855 Dec 74

T30177, an oligonucleotide composed of only deoxyguanosine and thymidine, is 17 nucleotides in length and contains single phosphorothioate internucleoside linkages at its 5' and 3' ends for stability. This oligonucleotide does not share significant primary sequence homology with or possess any complementary (antisense) sequence motifs to the human immunodeficiency virus type 1 (HIV-1) genome. T30177 inhibited replication of multiple laboratory strains of HIV-1 in human T-cell lines, peripheral blood lymphocytes, and macrophages. T30177 was also found to be capable of inhibiting multiple clinical isolates of HIV-1 and preventing the cytopathic effect of HIV-1 in primary CD4+ T lymphocytes. In assays with human peripheral blood lymphocytes there was no observable toxicity associated with T30177 at the highest concentration tested (100 microM), while the median inhibitory concentration was determined to be in the range of 0.1 to 1.0 microM for the clinical isolates tested, resulting in a high therapeutic index for this drug. In temporal studies, the kinetics of addition of T30177 to infected cell cultures indicated that, like the known viral adsorption blocking agents dextran sulfate and Chicago sky blue, T30177 needed to be added to cells during or very soon after viral infection. However, analysis of nucleic acids extracted at 12 h postinfection from cells treated with T30177 at the time of virus infection established the presence of unintegrated viral cDNA, including circular proviral DNA, in the treated cells. In vitro analysis of viral enzymes revealed that T30177 was a potent inhibitor of HIV-1 integrase, reducing enzymatic activity by 50% at concentrations in the range of 0.050 to 0.09 microM. T30177 was also able to inhibit viral reverse transcriptase activity; however, the 50% inhibitory value obtained was in the range of 1 to 10 microM, depending on the template used in the enzymatic assay. No observable inhibition of viral protease was detected at the highest concentration of T30177 used (10 microM). In experiments in which T30177 was removed from infected cell cultures at 4 days post-HIV-1 infection, total suppression of virus production was observed for more than 27 days. PCR analysis of DNA extracted from cells treated in this fashion was unable to detect the presence of viral DNA 11 days after removal of the drug from the infected cell cultures. The ability of T30177 to inhibit both laboratory and clinical isolates of HIV-1 and the experimental data which suggest that T30177 represents a novel class of integrase inhibitors indicate that this compound is a viable candidate for evaluation as a therapeutic agent against HIV-1 in humans.
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PMID:T30177, an oligonucleotide stabilized by an intramolecular guanosine octet, is a potent inhibitor of laboratory strains and clinical isolates of human immunodeficiency virus type 1. 858 21

Viral infection, especially by enteroviruses, has been considered to be the most common cause of myocarditis, which may progress to dilated cardiomyopathy (DCM). Although the mechanism of progression remains uncertain, a cytokine-associated injury of myocytes has been proposed. Using reverse transcriptase polymerase chain reaction (RT-PCR), we examined the expression of interleukin 1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor alpha (TNF-alpha) and the presence of enteroviral genomic RNA in endomyocardial biopsy tissues obtained from patients with myocarditis and DCM. We examined endomyocardial biopsy tissues obtained from 6 patients with myocarditis, 21 with DCM and 15 with non-infectious cardiac diseases as controls. In patients with myocarditis, endomyocardial biopsy was performed twice at an interval of 1 month to 8 years after the onset of myocarditis. We used RT-PCR to detect IL-1 beta, IL-6, IL-8 and TNF-alpha genes expression and nested RT-PCR (nRT-PCR) to detect enteroviral genomic RNA. IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in 100% (6/6) and enteroviral genomic RNA in 67% (4/6) of myocarditis patients at the first biopsy. At the second biopsy, IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in none, 50% (3/6), 67% (4/6) and 67% (4/6), respectively, and enteroviral genomic RNA in 67% (4/6). Four patients with myocarditis, in whom IL-8 and TNF-alpha genes and enteroviral genomic RNA were detected, progressed to DCM at the second biopsy. IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in none, 24% (5/21), 38% (8/21), 57% (12/21) of DCM patients, respectively. Enteroviral genomic RNA was detected in 43% (9/21) of DCM. Neither cytokine expression nor enteroviral genomic RNA were detected in the controls. the high incidence of cytokines, especially IL-6, IL-8 and TNF-alpha, expression in myocarditis and DCM, which might be induced by enteroviral infection, suggests that cytokines play an important role in myocytic damage leading to DCM.
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PMID:Expression of cytokine genes and presence of enteroviral genomic RNA in endomyocardial biopsy tissues of myocarditis and dilated cardiomyopathy. 862 80


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