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  • 1
    In: Genomics, Elsevier BV, Vol. 12, No. 3 ( 1992-3), p. 430-434
    Materialart: Online-Ressource
    ISSN: 0888-7543
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1992
    ZDB Id: 1468023-3
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Springer Science and Business Media LLC ; 1991
    In:  Nature Vol. 352, No. 6337 ( 1991-8), p. 725-728
    In: Nature, Springer Science and Business Media LLC, Vol. 352, No. 6337 ( 1991-8), p. 725-728
    Materialart: Online-Ressource
    ISSN: 0028-0836 , 1476-4687
    RVK:
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 1991
    ZDB Id: 120714-3
    ZDB Id: 1413423-8
    SSG: 11
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Cell, Elsevier BV, Vol. 57, No. 4 ( 1989-05), p. 659-666
    Materialart: Online-Ressource
    ISSN: 0092-8674
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1989
    ZDB Id: 187009-9
    ZDB Id: 2001951-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Journal of the American College of Surgeons Vol. 227, No. 4 ( 2018-10), p. e143-e144
    In: Journal of the American College of Surgeons, Ovid Technologies (Wolters Kluwer Health), Vol. 227, No. 4 ( 2018-10), p. e143-e144
    Materialart: Online-Ressource
    ISSN: 1072-7515
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2018
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    The Company of Biologists ; 1994
    In:  Journal of Experimental Biology Vol. 196, No. 1 ( 1994-11-01), p. 51-57
    In: Journal of Experimental Biology, The Company of Biologists, Vol. 196, No. 1 ( 1994-11-01), p. 51-57
    Kurzfassung: The molecular cloning of genes that encode amino acid transporters presents the scientific community with the opportunity to name their gene products using a scheme that could usefully recall the well-defined transport system most similar in properties to the newly identified cloned gene product. To avoid the problem of rising confusion, we propose to take advantage of established designation methods that indicate the types of amino acids transported and the co-substrate ion requirement of their transport. The economy obligated by the necessity to keep the number of symbols in a gene name to a minimum will rarely permit a listing of the full range of substrates, since amino acid transport systems have broad substrate specificities with co-substrate requirements that can differ in a substrate-specific manner. Hence, the use of established systems to codify groups of amino acid transport systems, which allow identification of the substrate range by using 1–3 letters, e.g. A, L or even ASC, could be integrated with a system used to indicate the ion-dependence of transport. The discoverers of transporters are mainly proceeding with commendable reserve and are inviting discussion, a desire which this essay urges be facilitated by more formal arrangements for further planning. These discoverers have also shown, along with an expressed desire for guidance, well-advised spontaneity in making reference to the substrate range, two trends that together suggest that a good set of designations can evolve that will be highly descriptive. We propose that this can be accomplished without a struggle to accommodate awkwardly to the requirements of the huge human genome data base cataloging system, nor to any single comprehensive systematic scheme. Instead, a combined scheme that takes into account the biological and biochemical characteristics, as well as the historical designations, of amino acid transport systems, is offered here for evaluation.
    Materialart: Online-Ressource
    ISSN: 0022-0949 , 1477-9145
    Sprache: Englisch
    Verlag: The Company of Biologists
    Publikationsdatum: 1994
    ZDB Id: 1482461-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Microbiology Society ; 2008
    In:  Journal of General Virology Vol. 89, No. 4 ( 2008-04-01), p. 1049-1058
    In: Journal of General Virology, Microbiology Society, Vol. 89, No. 4 ( 2008-04-01), p. 1049-1058
    Kurzfassung: Efforts to achieve cell type-specific transduction of retroviral vectors for gene therapy have centred on modification of the envelope protein (Env). Typically, addition of a ligand to Env gives binding to the new or target receptor, but little or no infection, and affects the subunit association of the modified Env. We previously discovered two point mutations that increase targeted infection by over 1000-fold when added to an Env modified by N-terminal insertion of the receptor-binding domain from amphotropic murine leukemia virus Env. Here, we asked whether these mutations would similarly increase transduction by Env modified with a clinically relevant ligand, human interleukin-13 (IL-13L). Addition of the point mutations stabilized the weak subunit association observed in some IL-13L-modified Env proteins, but infection via the target IL-13 receptor still did not occur. Fluorescence-based cell–cell fusion assays and studies with a membrane-curving agent revealed that defects in membrane fusion differed with the site of ligand insertion. When IL-13 was inserted into the N terminus of Env, membrane fusion was blocked prior to membrane-lipid mixing, regardless of whether flanking flexible linkers were added. Unexpectedly, insertion of IL-13 in the proline-rich region showed evidence of initiation of fusion and fusion-peptide exposure, but fusion was blocked at a subsequent step prior to fusion-pore formation. Thus, the site of ligand insertion influenced initiation of membrane fusion and its progression. These observations suggest that a novel site for ligand insertion must be identified before clinically useful targeted transduction will be achieved.
    Materialart: Online-Ressource
    ISSN: 0022-1317 , 1465-2099
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Microbiology Society
    Publikationsdatum: 2008
    ZDB Id: 2007065-2
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    American Society for Microbiology ; 1999
    In:  Journal of Virology Vol. 73, No. 7 ( 1999-07), p. 5621-5629
    In: Journal of Virology, American Society for Microbiology, Vol. 73, No. 7 ( 1999-07), p. 5621-5629
    Kurzfassung: It is thought that complete cleavage of retroviral envelope protein into mature surface protein (SU) and transmembrane protein (TM) is critical for its assembly into virions and the formation of infectious virus particles. Here we report the identification of highly infectious, cleavage-deficient envelope mutant proteins. Substitution of aspartate for lysine 104, arginines 124 and 126, or arginines 223 and 225 strongly suppressed cleavage of the envelope precursor and yet allowed efficient incorporation of precursor molecules as the predominant species in virions that were almost as infectious as the wild-type virus. These results indicate that cleavage of the envelope precursor into mature SU and TM is not necessary for assembly into virions. Moreover, they call into question how many mature envelope protein subunits are required to complete virus entry, suggesting that a very few molecules suffice. The failure of host cell proteases to cleave these mutant proteins, whose substitutions are distal to the actual site of cleavage, suggests that the envelope precursor is misfolded, sequestering the cleavage site. In agreement with this, all cleavage mutant proteins exhibited significant losses of receptor binding, suggesting that these residues play roles in proper envelope protein folding. We also identified a charged residue, arginine 102, whose substitution suppressed envelope cleavage and allowed precursor incorporation but resulted in virions that were virtually noninfectious and that exhibited the greatest reduction in receptor binding. Placement of these cleavage mutations into envelope proteins of targeted retroviral vectors for human gene therapy may prevent loss of the modified surface proteins from virions, improving their infectivity and storage hardiness.
    Materialart: Online-Ressource
    ISSN: 0022-538X , 1098-5514
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 1999
    ZDB Id: 1495529-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    American Society for Microbiology ; 2004
    In:  Journal of Virology Vol. 78, No. 1 ( 2004-01), p. 473-481
    In: Journal of Virology, American Society for Microbiology, Vol. 78, No. 1 ( 2004-01), p. 473-481
    Kurzfassung: The transmembrane subunits of viral envelope proteins are thought to perform all of the functions required for membrane fusion during entry of enveloped viruses. However, changes in a conserved SPHQ motif near the N terminus of the receptor binding subunit of a murine leukemia virus (MLV) envelope protein block infection and induction of cell-cell fusion but not receptor binding. Here we report evidence that a histidine-to-arginine change at position 8 (H8R) in the SPHQ motif of Moloney MLV blocks infection by arresting virus-cell fusion at the hemifusion state. In cell-cell fusion assays, H8R envelope protein induced mixing of membrane outer leaflet lipids but did not lead to content mixing, a finding indicative of fusion pore formation. Kinetic studies of virus-cell fusion showed that lipid mixing of H8R virus membranes begins much later than for wild-type virus. The length of the delay in lipid mixing decreased upon addition of two second-site changes that increase H8R virus infection to 100-fold less than the wild-type virus. Finally, chlorpromazine, dibucaine, and trifluoperazine, agents that induce pores in an arrested hemifusion state, rescued infection by H8R virus to within 2.5-fold of the level of wild-type virus infection and cell-cell fusion to half that mediated by wild-type envelope protein. We interpret these results to indicate that fusion progressed to the hemifusion intermediate but fusion pore formation was inhibited. These results establish that membrane fusion of Moloney MLV occurs via a hemifusion intermediate. We also interpret these findings as evidence that histidine 8 is a key switch-point residue between the receptor-induced conformation changes that expose fusion peptide and those that lead to six-helix bundle formation.
    Materialart: Online-Ressource
    ISSN: 0022-538X , 1098-5514
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2004
    ZDB Id: 1495529-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: Journal of Virology, American Society for Microbiology, Vol. 77, No. 11 ( 2003-06), p. 6341-6350
    Kurzfassung: Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung cancer of sheep known as ovine pulmonary adenocarcinoma (OPA). Expression of the JSRV envelope protein (Env) is sufficient to transform immortalized and primary fibroblasts, but the precise mechanisms of this process are not known. The cellular receptor for JSRV is hyaluronidase 2 (Hyal-2), the product of a putative tumor suppressor gene that in humans maps to a chromosomal region frequently deleted in the development of lung and breast cancers. Here we report studies to determine whether the Hyal-2-JSRV Env interaction plays a role in virus-induced transformation of rodent fibroblasts. Chimeric Env proteins between JSRV and the unrelated murine retroviruses Moloney murine leukemia virus (MMuLV) and mouse mammary tumor virus (MMTV) showed cell surface expression comparable to that of wild-type MMuLV Env and rescued infection of MMuLV particle pseudotypes. Interestingly, an MMuLV-JSRV chimera in which the putative receptor binding domain (RBD) and proline-rich region (PRR) of JSRV Env were replaced by the RBD and PRR of MMuLV induced transformation of 208F, a rodent fibroblast line. Cell lines derived from foci of MMuLV-JSRV chimera-transformed 208F cells grew in soft agar and showed Akt activation, a hallmark of JSRV-transformed rodent fibroblasts. Transformation assays performed using proteins with amino-terminal deletion mutations showed that the carboxy-terminal 141 amino acids of the transmembrane subunit (TM) were sufficient to induce cell transformation when targeted to the membrane with a myristoylation signal. Thus, the JSRV TM is necessary and sufficient to transform rodent fibroblasts. Taken together these results indicate that the interaction with Hyal-2 at least is not an essential determinant of JSRV-induced transformation of fibroblasts and that the viral TM functions essentially as an oncoprotein.
    Materialart: Online-Ressource
    ISSN: 0022-538X , 1098-5514
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 2003
    ZDB Id: 1495529-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    American Society for Microbiology ; 1999
    In:  Journal of Virology Vol. 73, No. 6 ( 1999-06), p. 5034-5042
    In: Journal of Virology, American Society for Microbiology, Vol. 73, No. 6 ( 1999-06), p. 5034-5042
    Kurzfassung: Entry of ecotropic murine leukemia virus initiates when the envelope surface protein recognizes and binds to the virus receptor on host cells. The envelope transmembrane protein then mediates fusion of viral and host cell membranes and penetration into the cytoplasm. Using a genetic selection, we isolated an infectious retrovirus variant containing three changes in the surface protein—histidine 8 to arginine, glutamine 227 to arginine, and aspartate 243 to tyrosine. Single replacement of histidine 8 with arginine (H8R) resulted in almost complete loss of infectivity, even though the mutant envelope proteins were stable and efficiently incorporated into virions. Virions carrying H8R envelope were proficient at binding cells expressing receptor but failed to induce cell-cell fusion of XC cells, indicating that the histidine at position 8 plays an essential role in fusion during penetration of the host cell membrane. Thus, there is at least one domain in SU that is involved in fusion; the fusion functions do not reside exclusively in TM. In contrast, envelope with all three changes induced cell-cell fusion of XC cells and produced virions that were 10,000-fold more infectious than those containing only the H8R substitution, indicating that changes at positions 227 and 243 can suppress a fusion defect caused by loss of histidine 8 function. Moreover, the other two changes acted synergistically, indicating that both compensate for the loss of the same essential function of histidine 8. The ability of these changes to suppress this fusion defect might provide a means for overcoming postbinding defects found in targeted retroviral vectors for use in human gene therapy.
    Materialart: Online-Ressource
    ISSN: 0022-538X , 1098-5514
    Sprache: Englisch
    Verlag: American Society for Microbiology
    Publikationsdatum: 1999
    ZDB Id: 1495529-5
    Standort Signatur Einschränkungen Verfügbarkeit
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