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)

Human immunodeficiency virus (HIV) gp120 induces multiple cellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3-kinase) pathway. The role of the PI3-kinase pathway in HIV-1 replication is not understood. Here we examined whether HIV-1 gp120 upregulates the PI3-kinase pathway and whether PI3-kinase activity plays a role in virus replication in primary human CD4(+) T cells and macrophages. Soluble and virion-associated HIV-1 gp120 induced calcium mobilization and phosphorylation of the PI3-kinase downstream effectors PKB/Akt and p70 S6 kinase. gp120-induced PI3-kinase activity and calcium mobilization were inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that the signaling is mediated through the chemokine receptor. The PI3-kinase inhibitor LY294002 inhibited infection of CD4(+) T cells and macrophages with X4 and R5 HIV-1-pseudotyped viruses at concentrations that did not induce cell toxicity or downregulate HIV-1 coreceptor expression. When gp120-induced signaling was bypassed with the vesicular stomatitis virus G envelope protein, infection was still sensitive to PI3-kinase inhibition, suggesting that basal PI3-kinase activity is required for infection. LY294002 inhibited HIV-1 infection when added after viral entry and did not affect formation of the HIV-1 reverse transcriptase products R/U5 and long terminal repeat/Gag in the presence of the inhibitor. However, when the inhibitor was added after viral integration had occurred, no inhibition of HIV infection was observed. Our studies show that inhibition of the PI3-kinase signaling pathway suppresses virus infection post-viral entry and post-reverse transcription but prior to HIV gene expression. This type of host-virus interaction has implications for anti-HIV therapeutics that target cellular signaling machinery.
...
PMID:Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages. 1255 92

Resting CD4(+) T cells containing integrated HIV provirus constitute one of the long-lived cellular reservoirs of HIV in vivo. This cellular reservoir of HIV had been thought to be quiescent with regard to virus replication based on the premise that HIV production in T cells is inexorably linked to cellular activation as determined by classical activation markers. The transition of T cells within this HIV reservoir from a resting state to an activated HIV-producing state is believed to be associated with a shorten life span due to susceptibility to activation-associated apoptosis. Evidence is mounting, however, that HIV production may occur in T cells that have not undergone classic T cell activation. HIV encodes several proteins, including envelope and Nef, which trigger a variety of signaling pathways associated with cellular activation, thereby facilitating HIV replication in nondividing cells. The present study demonstrates that production of infectious virus from resting CD4(+) T cells isolated from HIV-infected individuals can be induced following exposure of these cells to HIV-1 recombinant (oligomeric gp140) envelope protein. Envelope-mediated induction of HIV expression occurs in the presence of reverse transcriptase inhibitors and is not associated with markers of classic T cell activation, proliferation, or apoptosis. The ability of HIV envelope to induce virus replication in HIV-infected resting CD4(+) T cells without triggering apoptosis provides a mechanism for the virus itself to directly participate in the maintenance of HIV production from this cellular reservoir.
...
PMID:HIV envelope induces virus expression from resting CD4+ T cells isolated from HIV-infected individuals in the absence of markers of cellular activation or apoptosis. 1259 69

The genome of Schistosoma mansoni contains a proviral form of a retrovirus-like long terminal repeat (LTR) retrotransposon, designated BOUDICCA: Sequence and structural characterization of the new mobile genetic element, which was found in bacterial artificial chromosomes prepared from S. mansoni genomic DNA, revealed the presence of three putative open reading frames (ORFs) bounded by direct LTRs of 328 bp in length. ORF1 encoded a retrovirus-like major homology region and a Cys/His box motif, also present in Gag polyproteins of related retrotransposons and retroviruses. ORF2 encoded enzymatic domains and motifs characteristic of a retrovirus-like polyprotein, including aspartic protease, reverse transcriptase, RNase H, and integrase, in that order, a domain order similar to that of the gypsy/Ty3 retrotransposons. An additional ORF at the 3' end of the retrotransposon may encode an envelope protein. Phylogenetic comparison based on the reverse transcriptase domain of ORF2 confirmed that Boudicca was a gypsy-like retrotransposon and showed that it was most closely related to CsRn1 from the Oriental liver fluke Clonorchis sinensis and to kabuki from Bombyx mori. Bioinformatics approaches together with Southern hybridization analysis of genomic DNA of S. mansoni and the screening of a bacterial artificial chromosome library representing approximately 8-fold coverage of the S. mansoni genome revealed that numerous copies of Boudicca were interspersed throughout the schistosome genome. By reverse transcription-PCR, mRNA transcripts were detected in the sporocyst, cercaria, and adult developmental stages of S. mansoni, indicating that Boudicca is actively transcribed in this trematode.
...
PMID:Boudicca, a retrovirus-like long terminal repeat retrotransposon from the genome of the human blood fluke Schistosoma mansoni. 1274 72

Progesterone has been shown to regulate a number of genes and gene networks in the primate endometrium. This action of progesterone is essential to provide an appropriate milieu for embryo-endometrial communication that can lead to implantation and the successful initiation of pregnancy. A temporal regulation of endometrial genes is most likely required to achieve an appropriate state of receptivity in the primate endometrium. Using simulated menstrual cycles in the rhesus monkey, endometrial tissue was harvested at days that encompass the expected window of receptivity (4-10 days after the estradiol surge) and subsequently converted to cycle day-specific cDNA populations. Using differential display reverse transcriptase-polymerase chain reaction, 12 cDNA fragments were isolated and sequenced whose mRNA levels were elevated during this time frame. The temporal expression patterns of these mRNAs were confirmed by semiquantitative polymerase chain reaction. Two of these fragments exhibited high homology to previously characterized human genes: 1) secretory leukocyte protease inhibitor, also known as antileukoprotease, an endometrial neutrophil elastase inhibitor with antibacterial and anti-inflammatory properties; and 2) syncytin, also known as endogenous retrovirus W envelope protein, a highly fusogenic membrane glycoprotein that induces formation of giant syncytia and is believed to be important in decidual and placental development. The temporal regulation of these genes by progesterone supports their likely role in the orchestration of molecular and cellular events that are required to achieve a state of receptivity in the primate endometrium.
...
PMID:Temporal regulation of gene expression during the expected window of receptivity in the rhesus monkey endometrium. 1285 98

Acquired immunodeficiency syndrome (AIDS) is a worldwide epidemic caused by infection with HIV, a human retrovirus. Proteolysis occurs at many points of the retroviral life-cycle, and these events can be considered as targets for chemotherapy. The most well-known proteolytic action in the retroviral life-cycle is the processing of the Gag and Gag-Pro-Pol polyproteins with the virally encoded protease at the late phase of viral infection. Protease inhibitors, together with reverse transcriptase inhibitors, are important components of the drug combinations currently used to treat HIV patients. The current combination therapy substantially reduced morbidity and mortality in HIV-infected patients. However, these drugs do not allow viral eradication, therefore their long-term use is required, allowing the development of resistance in a large portion of patients. Furthermore, several adverse metabolic side effects have been observed associated with the therapy. Thus, new approaches are required to eradicate HIV infection, which may include targeting of the potential early-phase function of the viral protease, and other crucial proteolytic events of the viral replication, such as the ubiquitin-dependent proteolytic degradation of the unfolded viral proteins as well as the inhibition of envelope protein processing.
...
PMID:Proteolytic events of HIV-1 replication as targets for therapeutic intervention. 1287 Nov 98

For HIV-1 to enter a cell, its envelope protein (Env) must sequentially engage CD4 and a chemokine coreceptor, triggering conformational changes in Env that ultimately lead to fusion between the viral and host cell membranes. Each step of the virus entry pathway is a potential target for novel antiviral agents termed entry inhibitors. A growing number of entry inhibitors are under clinical development, with one having already been licensed by the Food and Drug Administration. With the emergence of virus strains that are largely resistant to existing reverse transcriptase and protease inhibitors, the development of entry inhibitors comes at an opportune time. Nonetheless, because all entry inhibitors target in some manner the highly variable Env protein of HIV-1, there are likely to be challenges in their efficient application that are unique to this class of drugs. Env density, receptor expression levels, and differences in affinity and receptor presentation are all factors that could influence the clinical response to this promising class of new antiviral agents.
...
PMID:The entry of entry inhibitors: a fusion of science and medicine. 1296 Mar 67

Recombinant rabies virus (RV) vaccine strain-based vectors have been successfully developed as vaccines against other viral diseases (J. P. McGettigan et al., J. Virol. 75:4430-4434, 2001; McGettigan et al., J. Virol. 75:8724-8732, 2001; C. A. Siler et al., Virology 292:24-34, 2002), and safety concerns have recently been addressed (McGettigan et al., J. Virol. 77:237-244, 2003). However, size limitations of the vectors may restrict their use for development of vaccine applications that require the expression of large and multiple foreign antigens. Here we describe a new RV-based vaccine vehicle expressing 4.4 kb of the human immunodeficiency virus type 1 (HIV-1) Gag-Pol precursor Pr160. Our results indicate that Pr160 is expressed and processed, as demonstrated by immunostaining and Western blotting. Electron microscopy studies showed both immature and mature HIV-1 virus-like particles (VLPs), indicating that the expressed HIV-1 Gag Pr55 precursor was processed properly by the HIV-1 protease. A functional assay also confirmed the cleavage and functional expression of the HIV-1 reverse transcriptase (RT) from the modified RV genome. In the next step, we constructed and recovered a new RV vaccine strain-based vector expressing a chimeric HIV-1(89.6P) RV envelope protein from an additional RV transcription unit located between the RV nucleoprotein (N) and phosphoprotein (P) in addition to HIV-1 Pr160. The 2.2-kb chimeric HIV-1/RV envelope protein is composed of the HIV-1 Env ectodomain (ED) and transmembrane domain (TD) fused to RV glycoprotein (G) cytoplasmic domain (CD), which is required for efficient incorporation of HIV-1 Env into RV particles. Of note, the expression of both HIV-1 Env and HIV-1 Pr160 resulted in an increase in the rhabdoviral genome of >55%. Both rhabdovirus-expressed HIV-1 precursor proteins were functional, as indicated by RT activity and Env-based fusion assays. These findings demonstrate that both multiple and very large foreign genes can be effectively expressed by RV-based vectors. This research opens up the possibility for the further improvement of rhabdovirus-based HIV-1 vaccines and their use to express large foreign proteins, perhaps from multiple human pathogens.
...
PMID:Functional human immunodeficiency virus type 1 (HIV-1) Gag-Pol or HIV-1 Gag-Pol and env expressed from a single rhabdovirus-based vaccine vector genome. 1451 39

The possibility of genomic recombination among different strains of infectious bronchitis virus (IBV) was examined in eve by coinfecting specific pathogen free embryonating chicken eggs with commonly used, embryo-adapted vaccine strains of IBV (Arkansas, Massachusetts, and Connecticut), and a Delaware-072-like field virus isolated from a layer farm in Minnesota. Recombination was observed between th e Massachusetts and the Delaware-072-like strains of the virus. The recombination event was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) using a combination of specific primers designed to flank a known recombination hot spot of the viral genomic sequence that codes for the S1 subunit of the spike envelope protein. The use of these primers allowed the detection of viruses that have undergone recombination around this hot spot. Cloning and sequencing of the RT-PCR product obtained was performed to confirm these results.
...
PMID:A recombination event, induced in ovo, between a low passage infectious bronchitis virus field isolate and a highly embryo adaptedvaccine strain. 1470 73

It is unknown whether all hepatitis C virus (HCV) quasispecies variants found within patient serum have equal capacity to associate with the liver after transplantation; however, in vitro models of HCV infection suggest that variations in the hypervariable region 1 (HVR1) of the second envelope protein (E2) may be important in infectivity. The hypothesis of the current study is that the two hypervariable regions (HVR1 and HVR2) within E2 are important in the initial virus-liver interaction, and, therefore, certain HCV quasispecies variants will be isolated from the liver after reperfusion. In 8 patients with end-stage liver disease secondary to HCV infection, HCV envelope quasispecies were determined from intraoperative serum samples obtained before the anhepatic phase of transplantation and from liver biopsies 1.5 to 2.5 hours after the transplanted liver was perfused. Explanted (native) liver biopsies were taken as a control. Sequence analysis was performed on clones of specific HCV reverse transcriptase-polymerase chain reaction products spanning HVR1 and HVR2 of the E2 protein. HVR1 was more variable than HVR2 for all samples. Quasispecies isolated from postperfusion liver differed more from serum than did explanted liver quasispecies at HVR1 (P = 0.03) but not at HVR2 (P = 0.2). Comparison of HVR1 sequences from postperfusion liver versus serum revealed significantly less HVR1 genetic complexity and diversity (P = 0.02 and P = 0.04, respectively). Immediately after transplantation but before actual infection, liver allografts select out from the infecting serum inoculum a less heterogeneous, more closely related population of quasispecies variants.
...
PMID:E2 quasispecies specificity of hepatitis C virus association with allografts immediately after liver transplantation. 1476 58

It has been reported that high-pressure (over 600 MPa) treatment at room temperature inactivates human immunodeficiency virus type 1 (HIV-1), and it has recently been shown that the high pressure generated by the expansion of water due to freezing (freeze pressure generation method, or FPGM) has an inactivating effect on bacteria and fungi. In this study, we examined the effects of treatment by FPGM on HIV-1. A sturdy vessel filled with water and securely closed with a lid was kept at 0 degrees C to -30 degrees C. High pressures of 200 MPa and 250 MPa were generated at -20 degrees C and -30 degrees C, respectively. When T-cell-tropic and macrophage-tropic laboratory strains of HIV-1 were kept at -10 degrees C, the virus infectivity decreased to approximately 1/100, and was completely lost at -20 degrees C and -30 degrees C. Four T-cell-tropic and four macrophage-tropic laboratory strains and clinical isolates of HIV-1 became completely inactivated at -30 degrees C. Treatment by FPGM at -20 degrees C to -30 degrees C reduced HIV-1 reverse transcriptase activity to approximately one tenth. In addition, treatment by FPGM at -20 degrees C was found to destroy the ability of HIV-1 to bind to CD4+ cells. In conclusion, this study showed that treatment by FPGM at -20 degrees C to -30 degrees C destroyed the infectivity of a wide range of HIV-1 strains, and suggested that the mechanisms of HIV-1 inactivation were the reduction in viral enzyme activity and the loss of the cell-binding ability of a viral envelope protein.
...
PMID:Novel method of inactivation of human immunodeficiency virus type 1 by the freeze pressure generation method. 1570 Jan 26


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

---