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

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Freshly separated unfractionated peripheral blood mononuclear cells (PBMC) and cloned cell lines from a healthy human immunodeficiency virus 1 (HIV-1)-seropositive individual were examined for cytotoxic responses to HIV proteins expressed by recombinant vaccinia viruses. It was found that freshly isolated PBMC recognize variant envelope proteins of HIV-1 but not a more distantly related envelope protein derived from the simian immunodeficiency virus (SIVmac). Although the effector cells were predominantly CD8+, both MHC-matched and -unmatched target cells were lysed. Cytotoxic T lymphocyte (CTL) clones were found to lyse cells expressing HIV-1 envelope or reverse transcriptase. In contrast to the cytotoxic response detected with PBMC, the cloned CTLs were major histocompatibility complex (MHC) class I restricted. Our finding that a cloned CTL line lysed cells expressing highly divergent HIV envelopes strongly suggested that a conserved epitope was recognized. Identification of these shared epitopes may assist in designing a vaccine for HIV-1 that could stimulate MHC-restricted cytotoxic responses.
...
PMID:Group-specific, major histocompatibility complex class I-restricted cytotoxic responses to human immunodeficiency virus 1 (HIV-1) envelope proteins by cloned peripheral blood T cells from an HIV-1-infected individual. 246 Aug 73

In central equatorial Africa the frequency of uninterpretable or atypical Western blots (WB)--ie. antibodies to gag proteins only--can represent up to 50% of enzyme-linked immunosorbent assay (ELISA)-positive samples. To date the significance of such serology remains unknown. Nevertheless, an unusual HIV-1 strain has been isolated from the blood of a healthy Gabonese individual who presented an atypical WB. This virus, identified as isolated HIV-1OYl, grew to low titres of reverse transcriptase activity (less than 50,000 cpm/ml) and was not obviously cytopathic. Radioimmunoprecipitation and peptide ELISA studies indicated that the lack of env-specific reactivity was probably due to the absence of antibodies to the viral glycoproteins, rather than the virus encoding a highly divergent envelope protein. Molecular cloning and sequencing of the provirus proved it to be a string of HIV-1 which was genetically closer to European and North American than to African strains. Furthermore the envelope protein sequence contained all the features of a typical HIV-1 env gene. However, the tat gene derived from the proviral clone was functionally defective. Site-directed mutagenesis of this gene showed that this was due to the substitution of an essential cysteine residue for a serine. Polymerase chain reaction amplification of the tat gene, as well as parts of the gag and env gene sequences of HIV-1OYl, showed that essentially all of the proviruses were defective. These data emphasize the need to view HIV isolates as populations of distinct genomes capable of complementing each other.
...
PMID:A highly defective HIV-1 strain isolated from a healthy Gabonese individual presenting an atypical western blot. 255 49

The transmembrane glycoprotein (gp41) of human immunodeficiency virus type-1 (HIV-1) has a long cytoplasmic domain of unknown functional significance. To investigate the role of the carboxy-terminal (C-terminal) portion of the HIV-1 envelope protein in viral replication, infectivity, and cytopathogenicity, we examined the properties of a panel of mutants with variable deletions in the 3'-env region. Deletion of the C-terminal 76 amino acids did not abolish production of reverse transcriptase upon transfection of COS-1 cells. Deletion of the C-terminal 6-14 amino acids appeared sufficient to alter the replication pattern, infectivity, and cytopathogenicity of some clones. The data suggest that conformational determinants or specific sequences are responsible for the observed changes, rather than simply the length of the gp41 cytoplasmic tail.
...
PMID:Role of the carboxy-terminal portion of the HIV-1 transmembrane protein in viral transmission and cytopathogenicity. 278 44

Human retroviruses, or RNA viruses, including the 2 HIV agents associated with AIDS, and the 2 HTLV agents causing leukemia, are described from the viewpoint of history, detection, serology, transformation mechanism, disease pathophysiology, genetic function, associated disease, and related viruses. Both HTLV and HIV infect the human T-lymphocytes, also known as CD4 or helper cells. Both can now be grown in culture, and their genomes are well characterized. HTLV, an acronym for human T-lymphotropic leukemia virus, causes the fulminating adult T-cell leukemia-lymphoma (ATLL), 1st described in 1977. It is prevalent in population clusters, notably in the Caribbean and in southwestern Japan, and is spread by sexual, blood and perinatal routes, as is HIV. It is thought to promote transformation of target cells by release of growth promoting, soluble factor, perhaps a product of the viral "tat" gene. Besides leukemia, HTLV-1 causes a myelopathy sometimes called tropical spastic paraparesis. HIV, formerly known as HTLV-III, causes depletion of the T-cells, and also infects the brain and nervous system. IT has also been isolated from semen, cervical secretions, saliva, monocytes, milk, endothelial cells, tears and cornea. HIV has 5 more genes than HTLV, which regulate transcription, mRNA processing and virus maturation. Parts of the HIV genome are highly heterogeneous, and mutate rapidly, notable sections of the envelope protein. Thus, HIV has 2 main subtypes, but others are known and probably exist. Approaches toward developing AIDS therapeutic agents as of 1987 are outlined: an effective drug should cross the blood-brain barrier. Several anti-viral drugs that block the enzyme reverse transcriptase area being investigated. Possible mechanisms for growth of Kaposi's sarcoma, activation of herpes type viruses, and animal viruses related to HTLV and HIV are discussed.
...
PMID:Retroviruses: new viral infections in man. 289 67

The titers and isotypes of antibodies to specific proteins of the human immunodeficiency virus were determined by Western blot analysis of sera from 107 homosexual men. Antibody titers were generally lower in sera from patients with the acquired immunodeficiency syndrome (AIDS) and in sera from men whose condition subsequently progressed to AIDS than in sera from men who had not progressed to AIDS. We found no evidence of isotypic prominence or restriction of the antibody response. In multivariate analysis, lower levels of CD4 helper cells were most highly associated with progression to AIDS. Lower antibody titers to the envelope protein gp110, the core protein p24, and the reverse transcriptase enzyme p51/65 were also predictive of progression to AIDS independent of their association with CD4 cell levels. These data suggest that differences in antibody levels are not simply a consequence of severe immunodeficiency but may be markers for control of infection.
...
PMID:Antibody response to human immunodeficiency virus in homosexual men. Relation of antibody specificity, titer, and isotype to clinical status, severity of immunodeficiency, and disease progression. 349 76

The current epidemic of acquired immunodeficiency syndrome (AIDS) poses a major threat to our population. Urgently needed are both a vaccine to prevent infection with the etiologic retrovirus, human immunodeficiency virus (HIV), and safe, effective antiviral agents to treat those individuals already infected. The elucidation of viral replicative mechanisms has allowed the development and testing of several agents active against HIV in vitro. Inhibitors of reverse transcriptase that have demonstrated activity include azidothymidine, phosphonoformate, antimoniotungstate (HPA-23), and suramin. Ribavirin and recombinant interferon alpha-A (IFN-alpha-A) also inhibit HIV replication, although their mechanisms of action are less clear. All of these compounds are undergoing early clinical trials in patients with HIV infection. The identification of immunogenic viral proteins may allow the development of one or more subunit vaccines against HIV. Studies are underway to clone appropriate viral genes and incorporate the expressed proteins into vectors for administration. Laboratory models, e.g., chimpanzees, will be inoculated with candidate vaccines and, if successful, this will be followed by clinical trials for safety and efficacy in appropriate human populations seronegative for HIV. Although important problems, such as virus envelope protein variability, need to be addressed, efforts to develop effective vaccines may well prove successful in the years ahead.
...
PMID:Prospects for the prevention and therapy of infections with the human immunodeficiency virus. 354 Nov 31

The sequence of the 1600 3' terminal nucleotides of the RNA of rubella virus was determined from cDNA synthesized from both virion and intracellular RNA using reverse transcriptase and an oligodeoxythymidine primer and cloned into a bacterial plasmid vector. This sequence contained the complete coding sequence for virion envelope protein E1 and a 57 nucleotide nontranslated region between the stop codon for E1 and the poly A tract. The predicted size for E1 was 481 amino acids and within this sequence were three potential N-linked glycosylation sites and a putative trans-membrane domain near the carboxy terminus. Immediately preceding the E1 coding region was a putative signal sequence. No homology was found at either the amino acid or nucleotide level between the region of the rubella virus genome sequenced and corresponding regions of the genomes of the alphaviruses, the other genus of the family Togaviridae for which sequence information has been obtained.
...
PMID:Molecular cloning and sequencing of the region of the rubella virus genome coding for glycoprotein E1. 375 48

The properties of the virus synthesized by each of three morphologically different cell lines originating from DBA/2J fetal liver cells transformed by the anemic strain of Friend leukemia virus in vitro were analyzed. The cells of line G-1 are malignant in syngeneic DBA/2 mice, grow in suspension, and are erythroid in origin. Cells of lines G-2 and G-3 are adherent, are epithelial in appearance, and produce no tumors in DBA/2J mice. Higher reverse transcriptase activity was detected in the culture fluid of lines G-2 and G-3, although virus from G-1 cells was more leukemogenic. Differences were also found in the virion density and size of the viral genome. RNA from the virions produced by G-2 and G-3 cells sedimented at 75 S in a sucrose gradient; virion RNA from G-1 cells sedmiented at 60 S. However, when subjected to polyacrylamide gel electrophoresis, all three virus strains showed identical RNA subunits with an estimated molecular weight of 2.6 X 10(6). Analysis of virion proteins by slab gel electrophoresis showed differences in envelope protein (gp71) components but not in the major core protein (p30). The properties of these viruses are stable and remain unchanged after passage in 3T3 cells.
...
PMID:Variations in properties of virus released from morphologically different cell lines transformed in vitro by Friend leukemia virus. 616 May 80

Visna virus is a retrovirus which replicates in fibroblast-like cells of the sheep choroid plexus through a lytic cycle. Visna virions contain three major low-molecular-weight proteins (p30, p16, and p14) which, together with the genomic RNA and several molecules of reverse transcriptase, constitute the core structure of the virions. The core is surrounded by an envelope containing a major glycoprotein (gp135). By analogy with the oncoviruses, these three groups of structural proteins (i.e., the internal proteins, the envelope glycoprotein, and the reverse transcriptase) are probably encoded by the gag, env, and pol genes, respectively. To elucidate the genetic organization of the visna virus genome and its expression, we studied the synthesis of viral proteins in infected sheep choroid plexus cells. Intracellular viral proteins were detected by immunoprecipitation of pulse-labeled cell extracts with monospecific sera raised against p30, p16, and gp135 and resolution of the proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoprecipitation with anti-p30 and anti-p16 sera allowed the characterization of the 55,000-dalton polypeptide precursor to internal virion proteins p30, p16, and p14 (Pr55(gag)). Tryptic peptide mapping confirmed the precursor-product relationship between Pr55(gag) and the three internal proteins. In addition, a gag-related polypeptide of 150,000 daltons was also detected. This polypeptide, which was less abundant than Pr55(gag), is a likely precursor to the viral reverse transcriptase (Pr150(gag-pol)). Pr55(gag) and Pr150(gag-pol) are not glycosylated. The precursor related to major envelope protein gp135 is a glycosylated polypeptide with an average molecular weight of 150,000 (gPr150(env)). Pulse-chase experiments indicated that gPr150(env) matures into glycoprotein gp135 intracellularly; however, gp135 was never preponderant in cell extracts. The non-glycosylated from of gPr150(env), which accumulated in the presence of 2-deoxy-d-glucose, appeared as a polypeptide of about 100,000 daltons. These results indicated that visna virus codes for the largest non-glycosylated env-related precursor among all of the retroviruses and therefore probably contains the largest env gene.
...
PMID:Precursor polypeptides to structural proteins of visna virus. 617 45

The synthesis and processing of B77 avian sarcoma virus RNA in infected chicken embryo fibroblasts was followed in the presence and absence of cycloleucine, a competitive inhibitor of the synthesis of S-adenosylmethionine and thus an inhibitor of RNA methylations. An increase in the steady-state levels of genome-length RNA and a decrease in the steady-state levels of subgenomic RNA molecules were obtained in the S-adenosylmethionine-depleted avian sarcoma virus-infected cells after 24 h of treatment with the inhibitor. The total number of virus-specific RNA molecules per cell, however, remained relatively constant under either condition. The production of newly synthesized virus-specific RNA in cycloleucine-treated and untreated cells infected with a transformation-defective strain of B77 avian sarcoma virus was followed as a function of [(3)H]uridine labeling time. The accumulation of radioactive genome-length 8.4-kilobase (kb) RNA continued in cycloleucine-treated cells, and virus particle production proceeded at normal rates as previously shown by incorporation of labeled nucleoside precursors or amino acids. In contrast, newly synthesized 3.5-kb subgenomic mRNA, the putative mRNA for the envelope protein precursor, failed to accumulate in the treated cells. The extent of the inhibition in the appearance of the radioactive 3.5-kb RNA was correlated with the extent of the inhibition of viral genomic and cellular mRNA methylations and was a function of the cycloleucine concentration. Under conditions in which the accumulation of 3.5-kb envelope protein mRNA was blocked by the cycloleucine treatment, there were significant increases in the rate of synthesis of the polypeptide products of the genome-length RNA, the precursors to the non-glycosylated gag proteins (Pr76(gag)), and the reverse transcriptase (Pr 180(gag pol)) relative to the rate of synthesis of the envelope protein precursor (gPr 92(env)). These results suggest that there is an S-adenosylmethionine requirement for the splicing, but not for the synthesis, packaging, or messenger function, of avian retrovirus genome-length RNA. Possible reasons for this requirement are discussed.
...
PMID:Accumulation of spliced avian retrovirus mRNA is inhibited in S-adenosylmethionine-depleted chicken embryo fibroblasts. 628 5


<< Previous 1 2 3 4 5 6 7 8 Next >>

---