Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed an ex vivo gene transfer technique to rabbit arterial wall using autologous smooth muscle cells (SMCs). SMCs were harvested from rabbit ear artery, transduced in vitro with vesicular stomatitis virus G-glycoprotein pseudotyped retrovirus or feline immunodeficiency virus (FIV) and returned to the adventitial surface of the carotid artery using a periadventitial silicone collar or collagen sheet placed around the artery. Beta-galactosidase (lacZ) and human apolipoprotein E3 (apoE3) cDNAs were used as transgenes. After retrovirus-mediated gene transfer of lacZ the selected cells implanted with high efficiency and expressed lacZ marker gene at a very high level 7 and 14 days after the operation. The level of lacZ expression decreased thereafter but was still detectable 12 weeks after the gene transfer, and was exclusively localized to the site of cell implantation inside the collar. Utilizing FIV vector expressing apoE3, low levels of apoE were measured from serum collected from a low-density lipoprotein receptor deficient Watanabe heritable hyperlipidemic rabbits 1 month after the gene transfer. The physiological effect of apoE expression was detected as transiently elevated serum cholesterol levels. The results indicate that the model can be used for high efficiency local gene transfer in arteries, e.g. during vascular surgery. The model is also valuable for studying expression, stability and safety of new gene transfer vectors and their expression products in vivo.
J Mol Cell Cardiol 2004 Mar
PMID:Feline immunodeficiency virus and retrovirus-mediated adventitial ex vivo gene transfer to rabbit carotid artery using autologous vascular smooth muscle cells. 1501 Feb 68

Recombinant DNA technology has permitted tremendous progression in delivering genes into cells; however, further advances in gene replacement techniques are needed prior to application to hematological diseases. One of the greatest obstacles to gene therapy in human hematopoietic stem cells is the lack of a defined protocol in humans and low transduction efficiency. Currently, murine leukemia virus (MuLV) is the most popular choice as a gene transfer vehicle but it cannot infect non-dividing cells. In our study, vesicular stomatitis G protein pseudotyped MuLV and HIV-1 were produced by a split gene transfection method. Mononuclear cells were separated from healthy human bone marrow and pre-stimulated with cytokines to form myeloid cell lineages. The cells were infected at different MOls with highly concentrated virus and infection rates were analyzed by flow cytometry and progenitor cell assays. eGFP expression was much higher when using HIV-1 system than when using MuLV. Progenitor cell assays agreed with the results obtained by FACS, but the difference was less great. We conclude that the lentiviral system is more suitable for gene transfer to hematopoietic progenitor cells probably because it stably infects both dividing and non-dividing cells. In addition, fibronectin was shown to improve the rate of infection with HIV-1.
Mol Cells 2004 Apr 30
PMID:A stable gene transfer system for hematopoietic progenitor cells from human bone marrow using pseudotyped retroviral vectors. 1517 45

Here, we successfully demonstrate expression of the EGFP (enhanced green fluorescence protein) gene in chickens using replication-defective MLV (murine leukemia virus)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G glycoprotein). The recombinant retrovirus was injected beneath the blastoderm of non-incubated chicken embryos (stage X). After 12 days incubation, all of the eight living embryos assayed were found to express this vector-encoded EGFP gene, which was under the control of the RSV (Rous Sarcoma Virus) promoter, in diverse organ tissues, including head, beak, neck, wing, hock, tail, toes, heart, amnion, and yolk sac. Surprisingly, despite the presumed cytotoxicity of EGFP, some embryos hatched and survived and these had prominent green fluorescent spots, both in internal organs and externally.
Mol Reprod Dev 2004 Aug
PMID:Retrovirus-mediated gene transfer and expression of EGFP in chicken. 1523 26

Prevailing evolutionary forces are typically deduced from the pattern of differences in synonymous and non-synonymous mutations, under the assumption of neutrality in the absence of amino acid change. We determined the complete sequence of ten vesicular stomatitis virus populations evolving under positive selection. A significant number of the mutations occurred independently in two or more strains, a process known as parallel evolution, and a substantial fraction of the parallel mutations were silent. Parallel evolution was also identified in non-coding regions. These results indicate that silent mutations can significantly contribute to adaptation in RNA viruses, and relative frequencies of synonymous and non-synonymous substitutions may not be useful to resolve their evolutionary history.
J Mol Biol 2004 Oct 01
PMID:Positive selection of synonymous mutations in vesicular stomatitis virus. 1536 70

Viral populations subjected to repeated genetic bottleneck accumulate deleterious mutations in a process known as Muller's ratchet. Asexual viruses, such as vesicular stomatitis virus (VSV) can recover from Muller's ratchet by replication with large effective population sizes. However, mutants with a history of bottleneck transmissions often show decreased adaptability when compared to non-bottlenecked populations. We have generated a collection of bottlenecked mutants and allowed them to recover by large population passages. We have characterized fitness changes and the complete genomes of these strains. Mutations accumulated during the operation of Muller's ratchet led to the identification of two potential mutational hot spots in the VSV genome. As in other viral systems, transitions were more common than transversions. Both back mutation and compensatory mutations contributed to recovery, although a significant level of fitness increase was observed in nine of the 13 bottlenecked strains with no obvious changes in the consensus sequence. Additional replication of three strains resulted in the fixation of single point mutations. Only two mutations previously found in non-bottlenecked, high-fitness populations that had been adapting to the same environment were identified in the recovered strains.
J Mol Biol 2004 Oct 01
PMID:Molecular basis of fitness loss and fitness recovery in vesicular stomatitis virus. 1536 71

Characterizing cellular factors involved in the life cycle of human immunodeficiency virus type 1 (HIV-1) is an initial step toward controlling replication of HIV-1. Actin polymerization mediated by the Arp2/3 complex has been found to play a critical role in some pathogens' intracellular motility. We have asked whether this complex also contributes to the viral life cycles including that of HIV-1. We have used both the acidic domains from actin-related protein (Arp) 2/3 complex-binding proteins such as the Wiscott-Aldrich syndrome protein (N-WASP) or cortactin, and siRNA directing toward Arp2 to inhibit viral infection. HIV-1, simian immunodeficiency virus (SIV), and intracellular mature vaccinia virus (IMV) were sensitive to inhibition of the Arp2/3 complex, whereas MLV, HSV-1, and adenovirus were not. Interestingly, pseudotyping HIV-1 with vesicular stomatitis virus G protein (VSV-G) overcame this inhibition. Constitutive inhibition of the Arp2/3 complex in the T-cell line H9 also blocked replication of HIV-1. These data suggested the existence of an Arp2/3 complex-dependent event during the early phase of the life cycles of both primate lentiviruses and IMV. Inhibiting the HIV-1's ability to activate Arp2/3 complex could be a potential chemotherapeutic intervention for acquired immunodeficiency syndrome (AIDS).
Mol Biol Cell 2004 Dec
PMID:Inhibiting the Arp2/3 complex limits infection of both intracellular mature vaccinia virus and primate lentiviruses. 1538 24

Interference with nucleocytoplasmic transport is a strategy employed by certain viruses to compromise host cellular function. While it has been shown that the matrix (M) protein of the vesicular stomatitis virus (VSV) inhibits nuclear export of host cell mRNAs, the underlying mechanism has not been fully established. Here we show that VSV M protein binds the mRNA export factor Rae1/mrnp41. A mutant of M protein defective in Rae1 binding is unable to inhibit mRNA nuclear export. We further show that increased expression of Rae1 fully reverts the inhibition of mRNA export induced by M protein or following virus infection. We found that Rae1 is induced by interferon-gamma, a cytokine that plays a critical role in the immune response to viruses, such as VSV. Thus, these results demonstrate that VSV M protein blocks mRNA export by disrupting Rae1 function, which can be reverted by induction of Rae1 expression.
Mol Cell 2005 Jan 07
PMID:VSV disrupts the Rae1/mrnp41 mRNA nuclear export pathway. 1562 20

Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. The results suggest that cholesterol is a rate-limiting component for caveolin trafficking. Changes in caveolin flux through the exocytic pathway can therefore be an indicator of cellular cholesterol and fatty acid levels.
Mol Biol Cell 2005 Apr
PMID:Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies. 1568 93

Constitutive activation of receptor tyrosine kinases (RTKs) is a frequent event in human cancer cells. Activating mutations in Fms-like tyrosine kinase 3 (FLT-3), notably, internal tandem duplications in the juxtamembrane domain (FLT-3 ITD), have been causally linked to acute myeloid leukemia. As we describe here, FLT-3 ITD exists predominantly in an immature, underglycosylated 130-kDa form, whereas wild-type FLT-3 is expressed predominantly as a mature, complex glycosylated 150-kDa molecule. Endogenous FLT-3 ITD, but little wild-type FLT-3, is detectable in the endoplasmic reticulum (ER) compartment. Conversely, cell surface expression of FLT-3 ITD is less efficient than that of wild-type FLT-3. Inhibition of FLT-3 ITD kinase by small molecules, inactivating point mutations, or coexpression with the protein-tyrosine phosphatases (PTPs) SHP-1, PTP1B, and PTP-PEST but not RPTPalpha promotes complex glycosylation and surface localization. However, PTP coexpression has no effect on the maturation of a surface glycoprotein of vesicular stomatitis virus. The maturation of wild-type FLT-3 is impaired by general PTP inhibition or by suppression of endogenous PTP1B. Enhanced complex formation of FLT-3 ITD with the ER-resident chaperone calnexin indicates that its retention in the ER is related to inefficient folding. The regulation of RTK maturation by tyrosine phosphorylation was observed with other RTKs as well, defines a possible role for ER-resident PTPs, and may be related to the altered signaling quality of constitutively active, transforming RTK mutants.
Mol Cell Biol 2005 May
PMID:Tyrosine phosphorylation regulates maturation of receptor tyrosine kinases. 1583 74

ISG15 is an interferon-induced ubiquitin-like modifier which can be conjugated to distinct, but largely unknown, proteins. ISG15 has been implicated in a variety of biological activities, which encompass antiviral defense, immune responses, and pregnancy. Mice lacking UBP43 (USP18), the ISG15-deconjugating enzyme, develop a severe phenotype with brain injuries and lethal hypersensitivity to poly(I:C). It has been reported that an augmented conjugation of ISG15 in the absence of UBP43 induces prolonged STAT1 phosphorylation and that the ISG15 conjugation plays an important role in the regulation of JAK/STAT and interferon signaling (O. A. Malakhova, M. Yan, M. P. Malakhov, Y. Yuan, K. J. Ritchie, K. I. Kim, L. F. Peterson, K. Shuai, and D. E. Zhang, Genes Dev. 17:455-460, 2003). Here, we report that ISG15(-/-) mice are viable and fertile and display no obvious abnormalities. Lack of ISG15 did not affect the development and composition of the main cellular compartments of the immune system. The interferon-induced antiviral state and immune responses directed against vesicular stomatitis virus and lymphocytic choriomeningitis virus were not significantly altered in the absence of ISG15. Furthermore, interferon- or endotoxin-induced STAT1 tyrosine-phosphorylation, as well as expression of typical STAT1 target genes, remained unaffected by the lack of ISG15. Thus, ISG15 is dispensable for STAT1 and interferon signaling.
Mol Cell Biol 2005 Aug
PMID:ISG15, an interferon-stimulated ubiquitin-like protein, is not essential for STAT1 signaling and responses against vesicular stomatitis and lymphocytic choriomeningitis virus. 1602 73


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