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 clinical significance and course of acute hepatitis G virus (HGV) infection were studied by measuring HGV RNA and antibody to HGV envelope protein E2 (HGV-E2 antibody). A total of 59 patients with transfusion-associated non-A, non-B hepatitis, who were followed-up for more than 1 year, were selected retrospectively. HGV RNA was measured by reverse transcriptase (RT) and nested polymerase chain reaction (PCR) was performed, using primer sets, in the 5'-non-coding region of the HGV genome. HGV-E2 antibody was measured by enzyme-linked immunosorbent assay (ELISA) using recombinant E2 protein. Of the 59 patients, 51 (86%) were infected with hepatitis C virus (HCV) and 12 (20%) were infected with HGV; 11 of the 12 with HGV infection were also infected with HCV. HGV viraemia was cleared during the follow-up period in seven of the 12 patients with HGV infection. All these seven patients seroconverted for HGV-E2 antibody just before or just after the clearance of HGV viraemia. In contrast, all five patients without clearance of HGV viraemia were negative for HGV-E2 antibody (P = 0.0013). Of seven patients with continuous HGV viraemia at 1 year from the onset of acute hepatitis, four with HCV RNA showed chronic elevation of alanine aminotransferase (ALT) but three without HCV RNA did not. The severity of acute hepatitis was similar between patients with both HGV and HCV infections and in those with HCV infection alone. The majority of patients with HGV infection cleared the virus during long-term follow-up. Appearance of HGV-E2 antibody was associated with the clearance of HGV viraemia. An abnormal ALT level was noted to depend on HCV infection but not on HGV infection in both the acute and chronic phases of transfusion-associated hepatitis.
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PMID:Evolution of hepatitis G virus infection and antibody response to envelope protein in patients with transfusion-associated non-A, non-B hepatitis. 965 67

Certain types of chemokine receptors have been identified as coreceptors for HIV-1 infection. The process of viral entry is initiated by the interaction between an envelope protein gp120 of HIV-1, CD4, and one of the relevant coreceptors. To understand the precise mechanism of the Env-mediated fusion and entry of HIV-1, we examined whether the V3 region of gp120 of T-cell line tropic (T-tropic) virus directly interacts with the coreceptor, CXCR-4, by using five synthetic V3 peptides: two cyclized V3 peptides (V3-BH10 and V3-ELI) which correspond to the V3 regions of the T-tropic HIV-1 IIIB and HIV-1 ELI strains, respectively, a linear V3 peptide (CTR36) corresponding to that of HIV-1 IIIB strain; and cyclized V3 peptides corresponding to that of the macrophage-tropic (M-tropic) HIV-1 ADA strain (V3-ADA) or the dualtropic HIV-1 89.6 strain (V3-89. 6). FACScan analysis with a CXCR-4(+) human B-cell line, JY, showed that V3-BH10, V3-ELI, and V3-89.6 but not CTR36 or V3-ADA blocked the binding of IVR7, an anti-CXCR-4 monoclonal antibody (MAb), to CXCR-4 with different magnitudes in a dose-dependent manner, while none of the V3 peptides influenced binding of an anti-CD19 MAb at all. Next, the effects of the V3 peptides on SDF-1beta-induced transient increases in intracellular Ca2+ were investigated. Three V3 peptides (V3-BH10, V3-ELI, and V3-89.6) prevented Ca2+ mobilization. Furthermore, the three peptides inhibited infection by T-tropic HIV-1 in a dose-dependent manner as revealed by an MTT assay and a reverse transcriptase assay, while the other peptides had no effects. These results present direct evidence that the V3 loop of gp120 of T-tropic HIV-1 can interact with its coreceptor CXCR-4 independently of the V1/V2 regions of gp120 or cellular CD4.
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PMID:T-tropic human immunodeficiency virus type 1 (HIV-1)-derived V3 loop peptides directly bind to CXCR-4 and inhibit T-tropic HIV-1 infection. 981 11

The human CXC chemokine receptor CXCR4 is activated by stromal cell-derived factor 1. The receptor is present in many cell types and regulates a variety of cellular functions, including chemotaxis, adhesion, hematopoiesis, and organogenesis. Human CXCR4 also serves as a cofactor for cell entry by certain strains of HIV-1 and HIV-2. In the mouse, alternative RNA splicing produces two transcripts encoding two CXCR4 isoforms, mCXCR4-A and mCXCR4-B, differing by the presence of two amino acids in the amino terminal portion of the longer protein, mCXCR4-B. Only one CXCR4 transcript, encoding the human counterpart of mCXCR4-A, is known in man. The involvement of the aminoterminal-most portion of CXCR4 in both ligand and HIV envelope protein recognition led us to determine whether a CXCR4 variant corresponding to mCXCR4-B is present in human tissues. To this end, the genomic organization and expression of the human CXCR4 gene was examined. Both the human and the mouse CXCR4 gene consist of two exons separated by an approximately 2.1 kbp intron between codons five and six and carry splice donor sites at the 5' end of their introns. These similarities notwithstanding, single nucleotide primer extension, reverse transcriptase PCR amplification, and sequencing of CXCR4 cDNA clones show that a splice variant of CXCR4 corresponding to mCXCR4-B is absent in man.
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PMID:Genomic organization and expression of the CXCR4 gene in mouse and man: absence of a splice variant corresponding to mouse CXCR4-B in human tissues. 987 64

HIV-1 retrovirus-like particles can be produced in VERO cells that have been transfected with an expression construct encoding HIV-1 structural proteins. The particles are entirely non-infectious although structurally they resemble infectious virus particles. This makes them a promising candidate for use as an HIV-1 vaccine. In order to ensure their safety and enhance their immunogenicity, the retrovirus-like particles were modified in a number of ways. A large deletion in the HIV-1 pol gene has eliminated reverse transcriptase and integrase activities. Deletion of RNA packaging signals in the RNA untranslated leader sequence and in Gag reduced packaged RNA to 5% of that in HIV-1 virus. Replacement of the existing HIV-1LAI envelope protein with that of HIV-1MN has ensured that immune responses to the particles are relevant to those against the majority of HIV-1 clade B isolates. In addition to these changes in particle composition, yields of the modified particles were increased using a superior method of inducing the expression construct promoter, and an effective scheme for particle purification was developed. Immunization of non-human primates demonstrated that the particles were capable of generating anti-HIV-1 neutralizing antibodies. The technological refinements reported here will permit retrovirus-like particles to be tested safely in humans, and the change in envelope proteins should allow a more realistic evaluation of the immunogenicity of these particles. Experience gained in engineering these refinements will greatly facilitate other modifications that may be required to achieve maximum efficacy as a vaccine against HIV-1.
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PMID:Modifications of HIV-1 retrovirus-like particles to enhance safety and immunogenicity. 1040 29

To determine whether there was a correlation between the kinetics or frequency of antibody to mammalian-derived hepatitis C virus (HCV) second envelope protein (E2) and development of chronicity or self-limitation of HCV infections, serial sera were examined for anti-E2, anti-HCV with confirmation with Matrix 2.0 (Abbott Laboratories, Abbott Park, IL), and reverse transcriptase-polymerase chain reaction (RT-PCR) from 6 cases of self-limited infection and 6 cases of chronic infection in chimpanzees, and from 5 cases of self-limited infection and 3 cases of chronic infection in patients. Anti-E2 developed earlier, more frequently, and to higher titer in chimpanzees and patients who were developing chronic infection than in those with self-limited infections. Thus anti-E2 is unlikely to play a role in self-limitation of the infection. However, long-term persistence of anti-E2 correlates with chronic infection. There was little or no correlation between the timing of development of anti-E2 and anti-HCV.
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PMID:Significance of the anti-E2 response in self-limited and chronic hepatitis C virus infections in chimpanzees and in humans. 1047 22

A human immunodeficiency virus (HIV) matrix (MA) protein mutant was constructed by duplication of 107 codons of the HIV-1 MA domain. This MA protein duplication mutant (MAII) still could assemble and process particles, had a wild-type (wt) HIV particle density, and possessed reverse transcriptase activity of about 80% of the wild type virus level. The incorporation of HIV Env and viral RNA genome was not greatly affected. The MAII was noninfectious or poorly infectious, however, when pseudotyped with an amphotropic murine leukemia virus envelope protein or with the HIV envelope protein. Although the MAII mutant displayed an immunofluorescence staining pattern similar to that of the wild type virus, subcellular fractionation studies indicated that the membrane association of MAII Gag precursors was unstable under high-salt conditions. Electron microscopic studies showed that the mutant had a decreased density of particle cores compared with that of the wild type virus, suggesting an altered arrangement of the packed proteins. As this insertion in the MA gene caused no major effects on virus assembly implies that the HIV-1 gag has the potential to adapt large insertions of extra coding sequences without loss of the ability to direct particle assembly and release.
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PMID:Analysis of a human immunodeficiency virus type 1 gag mutant with an engineered 110-amino-acid insertion in the matrix protein domain. 1089 59

The genome of an Australian strain of duck hepatitis B virus (AusDHBV) was cloned from a pool of congenitally DHBV-infected-duck serum, fully sequenced and found by phylogenetic analyses to belong to the 'Chinese' DHBV branch of the avian hepadnaviruses. Sequencing of the Pre-S/S gene of four additional AusDHBV clones demonstrated that the original clone (pBL4.8) was representative of the virus present in the pool, and a head-to-tail dimer of the clone was infectious when inoculated into newly hatched ducks. When the published sequences of 20 avian hepadnaviruses were compared, substitutions or deletions in the polymerase (POL) gene were most frequent in the 500 nt segment encoding the 'spacer' domain that overlaps with the Pre-S domain of the Pre-S/S gene in a different reading frame. In contrast, substitutions and deletions were rare within the adjacent segment that encodes the reverse transcriptase domain of the POL protein and the S domain of the envelope protein, presumably because they are more often deleterious.
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PMID:Sequence comparison of an Australian duck hepatitis B virus strain with other avian hepadnaviruses. 1116 Dec 76

Human immunodeficiency virus type 1 (HIV-1) Nef protein exerts several effects, both on infected cells and as a virion protein, which work together to enhance viral replication. One of these activities is the ability to enhance infectivity and the formation of proviral DNA. The mechanism of this enhancement remains incompletely understood. We show that virions with nef deleted can be restored to wild-type infectivity by stimulating intravirion reverse transcription. Particle composition and measures of reverse transcriptase activity remain the same for Nef(+) and Nef(-) virions both before and after natural endogenous reverse transcription (NERT) treatment. The effect of NERT treatment on virions pseudotyped with murine leukemia virus envelope protein was similar to that on particles pseudotyped with HIV-1 envelope protein. However, virions pseudotyped with vesicular stomatitis virus G envelope protein showed no influence of Nef on NERT enhancement of infectivity. These observations suggest that Nef may function at a level prior to reverse transcription. Since NERT treatment results in partial disassembly of the viral core, we speculate that Nef may function at the level of core particle disassembly.
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PMID:Restoration of wild-type infectivity to human immunodeficiency virus type 1 strains lacking nef by intravirion reverse transcription. 1171 98

The potential for hepatitis B virus (HBV) to alter its genome is considerable. This occurs because the virus utilizes a reverse transcription step in replicating the viral genome. Like human immunodeficiency virus, the reverse transcriptase of HBV is error prone and as a consequence of specific selection pressures within a host a population of viral quasispecies emerges. HBV mutants with survival advantages over the wild type virus appear within the selective in vivo environment. Some of these viruses include HBV vaccine escape and anti-viral resistant mutants that have changes in the envelope (S) and polymerase genes, respectively. In addition, the genome of HBV is organised in to overlapping reading frames. The S gene is completely overlapped by the polymerase gene. As a consequence, mutations in the S gene may produce changes in the overlapping polymerase gene. Similarly, mutations in the polymerase gene may produce changes in the S gene. The virological and clinical significance of such overlapping mutations is unclear. However, we have shown that certain mutations in either the S or polymerase gene produce functionally significant changes in the respective overlapping gene. Treatment of chronic hepatitis B carriers with long-term lamivudine (LMV) results in the selection of HBV mutants that are resistant to this nucleoside analogue. The polymerase mutations associated with LMV resistance produce changes in the overlapping S gene and in its envelope protein (hepatitis B small antigen, HBsAg) that results in a reduced antigenicity of the HBsAg protein. The selection of vaccine escape mutants by HBV vaccination or hepatitis B immune globulin is associated with changes in the S gene that are accompanied by mutations in the fingers sub-domain of the polymerase protein. When combined with polymerase mutations that are associated with resistance to LMV the changes within the fingers sub-domain of the viral enzyme behave as compensatory mutations that are able to restore the replication of LMV resistant HBV. The ability to change a viral protein by mutations in an overlapping but unrelated viral gene may produce HBV mutants with altered antigenicity and/or replication and a natural history that may be distinctly different to wild type HBV.
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PMID:The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis B virus. 1236 44

Highly active inhibitors of human immunodeficiency virus (HIV) reverse transcriptase and protease have made it possible to dramatically reduce virus load in HIV-positive individuals. However, the presence of viral reservoirs, the emergence of drug-resistant HIV variants and the side effects of these compounds call for research into new drugs that target different stages of the viral life cycle. One attractive target is the first step in HIV replication: entry of virus into cells. HIV entry is initiated by the attachment of the virus to the host cell membrane, which is some cases involves binding to attachment factors such as DC-SIGN. Subsequent interaction of the envelope protein (Env) with the CD4 receptor causes conformational changes that enable Env to interact with a coreceptor, generally the chemokine receptors CCR5 or CXCR4. Coreceptor engagement triggers the final conformational changes in Env, which mediate lipid mixing between the viral and cellular membranes. All of these steps are potential targets for therapeutic intervention: targeting proteins that mediate viral attachment may reduce HIV transmission, while receptor blockade will inhibit virus entry. Highly conserved domains in Env which bind to CD4 and coreceptor are promising targets for broadly neutralizing antibodies, and peptide inhibitors that bind to Env and that block membrane fusion are in advanced clinical trials. These new approaches may supplement current HIV therapy and may assist in the development of an HIV vaccine.
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PMID:Evaluation of current approaches to inhibit HIV entry. 1246 49


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