Search results for "Integrase"
showing 10 items of 49 documents
On the transposon origins of mammalian SCAND3 and KRBA2, two zinc-finger genes carrying an integrase/transposase domain
2012
SCAND3 and KRBA2 are two mammalian proteins originally described as “cellular-integrases” due to sharing of a similar DDE-type integrase domain whose origin and relationship with other recombinases remain unclear. Here we perform phylogenetic analyses of 341 integrase/transposase sequences to reveal that the integrase domain of SCAND3 and KRBA2 derives from the same clade of GINGER2, a superfamily of cut-and-paste transposons widely distributed in insects and other protostomes, but seemingly absent or extinct in vertebrates. Finally, we integrate the results of phylogenetic analyses to the taxonomic distribution of SCAND3 and KRBA2 and their transposon relatives to discuss some of the proce…
A mammalian gene evolved from the integrase domain of an LTR retrotransposon.
2001
FIG. 1.—Summary of the structure and coding sequence of the human Gin-1 gene. Sequences of human cDNAs with accession numbers XMp003947.2 (a putative full-length cDNA), BE502574, AW173201.1, AW950418.1, AI631948.1, and AA766836.1 were used to deduce and confirm these data. The full-length protein is 522 amino acids long. The Gin-1 coding region spans nucleotides 36153–15345 in the genomic clone NTp002663.4. Arrowheads and the numbers above them, respectively, indicate the positions and lengths of introns. Several Alu repeats were detected within the two largest introns. Bold letters indicate the region homologous to the most conserved part of the IN domain, detailed in figure 2 and used to …
Frequent coinfection of cells explains functional in vivo complementation between cytomegalovirus variants in the multiply infected host.
2005
In contrast to many other virus infections, primary cytomegalovirus (CMV) infection does not fully protect against reinfection. Accordingly, clinical data have revealed a coexistence of multiple human CMV variants/ strains in individual patients. Notably, the phenomenon of multiple infection was found to correlate with increased virus load and severity of CMV disease. Although of obvious medical relevance, the mechanism underlying this correlation is unknown. A weak immune response in an individual could be responsible for a more severe disease and for multiple infections. Alternatively, synergistic contributions of variants that differ in their biological properties can lead to qualitative…
Of mice and models: improved animal models for biomedical research.
2002
The ability to engineer the mouse genome has profoundly transformed biomedical research. During the last decade, conventional transgenic and gene knockout technologies have become invaluable experimental tools for modeling genetic disorders, assigning functions to genes, evaluating drugs and toxins, and by and large helping to answer fundamental questions in basic and applied research. In addition, the growing demand for more sophisticated murine models has also become increasingly evident. Good state-of-principle knowledge about the enormous potential of second-generation conditional mouse technology will be beneficial for any researcher interested in using these experimental tools. In thi…
Adverse drug reactions to antiretroviral medication
2009
Antiretroviral therapy has greatly improved prognosis of HIV infection, with a dramatic reduction of morbidity and mortality worldwide. Nevertheless, the condition is still a common cause of death in many underdeveloped countries, where effective treatment is not always unavailable. More than 20 drugs active against HIV are commercially available, which belong to one of four groups: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion/entry inhibitors. In the near future new drugs are expected, including those of a novel group, the integrase inhibitors. To avoid viral resistance, combinations of the drugs must always b…
Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice
2006
Background/Aims In hepatic fibrogenesis, stellate cells are activated leading to production and deposition of extracellular matrix. To clarify the role of PDGF-B in liver fibrogenesis, we overexpressed PDGF-B in the liver of transgenic mice. Methods Transgenic mice for the conditional overexpression of PDGF-B in the liver under control of an albumin promoter were generated utilising the Cre/loxP system. Constitutive PDGF-B expression was achieved after breeding with mice expressing Cre-recombinase under actin promoter control. Tamoxifen inducible expression was achieved after breeding with mice expressing Cre under transthyretin receptor promoter control. Levels of fibrosis were assessed an…
Toxicity of ligand-dependent Cre recombinases and generation of a conditional Cre deleter mouse allowing mosaic recombination in peripheral tissues.
2007
Ligand-activated Cre recombinases are widely used for studying gene function in vitro and in conditional mouse models. To compare ligand-dependent Cre recombinases, different Cre estrogen receptor fusions were introduced into the ROSA26 locus of embryonic stem (ES) cells and assayed for genotoxicity and recombination efficiency. Of the tested recombinases, the CreERT2 variant showed no toxicity and was highly responsive to ligand induction. To constitutively express CreERT2 in mice and also to clarify whether the CreERT2 system displays background activity, we generated a knock-in mouse line harboring the CreERT2 coding region under the control of the ROSA26 locus. Analysis of this ROSA26-…
Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors
2020
Abstract Objectives This study evaluated the emergence of mutations associated with integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in human immunodeficiency virus type 1 (HIV-1) infected patients treated with this drug class. Methods The emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under INSTI treatment and before INSTI treatment) were evaluated in 107 INSTI-naive patients (19 drug-naive and 88 drug-experienced) with two plasma genotypic resistance tests: one before INSTI treatment and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associ…
The Major Virus-Producing Cell Type during Murine Cytomegalovirus Infection, the Hepatocyte, Is Not the Source of Virus Dissemination in the Host
2008
SummaryThe course of systemic viral infections is determined by the virus productivity of infected cell types and the efficiency of virus dissemination throughout the host. Here, we used a cell-type-specific virus labeling system to quantitatively track virus progeny during murine cytomegalovirus infection. We infected mice that expressed Cre recombinase selectively in vascular endothelial cells or hepatocytes with a murine cytomegalovirus for which Cre-mediated recombination would generate a fluorescently labeled virus. We showed that endothelial cells and hepatocytes produced virus after direct infection. However, in the liver, the main contributor to viral load in the mouse, most viruses…
A restricted population of CB1 cannabinoid receptors with neuroprotective activity.
2014
The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown. Here, we first induced excitotoxic damage in the mouse brain b…