@article{SiwkaSchwinnBaczkoetal.1994, author = {Siwka, Wieslaw and Schwinn, Andreas and Baczko, Knut and Pardowitz, Iancu and Mhalu, Fred and Shao, John and Rethwilm, Axel and ter Meulen, Volker}, title = {vpu and env sequence variability of HIV-1 isolates from Tanzania}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61355}, year = {1994}, abstract = {No abstract available}, subject = {Virologie}, language = {en} } @phdthesis{Flechsig2011, author = {Flechsig, Christin}, title = {Untersuchung von Modifiziertem Vaccinia Ankara Virus (MVA) zur Induktion Cytomegalovirus (CMV) spezifischer T-Zell-Antworten}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57637}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Eine Infektion mit dem humanen Cytomegalievirus ist immer noch eine der h{\"a}ufigsten und bedrohlichsten Komplikationen nach einer allogenen Stammzelltransplantation (SCT), welche eine hohe Morbidit{\"a}t und Mortalit{\"a}t verursacht. Die prophylaktische oder pre{\"a}mptive antivirale Chemotherapie konnte den fr{\"u}hen Ausbruch einer CMV-Erkrankung w{\"a}hrend der ersten 100 Tage nach SCT signifikant reduzieren, jedoch kommt es dadurch h{\"a}ufig zu einem sp{\"a}ten Ausbruch der CMV-Erkrankung und schwerwiegenden Nebenwirkungen wie Myelotoxizit{\"a}t und Nephrotoxizit{\"a}t. Zur Bek{\"a}mpfung und Langzeitkontrolle einer CMV-Infektion ist eine effiziente zellvermittelte CMV-spezifische Immunit{\"a}t unabdingbar. Im Rahmen dieser Dissertation, wurden deshalb drei CMV-Vakzinkandidaten basierend auf dem hoch attenuierten Modifizierten Vaccinia Ankara Virus (MVA), welche stabil pp65 und/oder IE1 (MVA-IE1, MVA-pp65, and MVA-IE1-pp65) exprimieren und zugleich frei von Selektionsmarkern sind, auf ihre F{\"a}higkeit hin untersucht CMV-spezifische T-Zellantworten zu induzieren. Als erstes wurden humane mononukle{\"a}re Zellen des periph{\"a}ren Blutes (PBMCs) und Leukozytensubpopulationen (aus Monozyten generierte dendritische Zellen (DCs), Monozyten und B-Zellen) mit MVA infiziert um deren Infektionsrate, Ver{\"a}nderungen in der Expression der Oberfl{\"a}chenmarker und der Zytokinexpression sowie deren Apoptoserate zu untersuchen. Monozyten, DCs und B-Zellen waren besonders empf{\"a}nglich f{\"u}r eine MVA-Infektion, gefolgt von NK-Zellen. Monozyten wurden stark aktiviert, was sich durch eine erh{\"o}hte Expression der kostimulatorischen Molek{\"u}le, MHC-Komplexe und CCR7 zeigte, wohingegen DCs eine inkomplette Aktivierung vorwiesen und B-Zellen gehemmt wurden. Des Weiteren wurde die Expression von CXCL10, TNFa, IL-6 und IL-12 signifikant in den Antigen-pr{\"a}sentierenden Zellen (APCs) erh{\"o}ht, aber die von IL-1b und IL-10 blieb unver{\"a}ndert oder wurde sogar signifikant reduziert. MVA induzierte also eine Th1-polarisierenden Zytokinexpression in den APCs. Allerdings konnten CMV-spezifische T-Zellen nicht mit direkter Antigenpr{\"a}sentation durch DCs expandiert werden, da die DCs nach Infektion mit MVA schnell durch Apoptose starben und eine unzureichende Expression der kostimulatorischen Molek{\"u}le und MHC-Komplexe aufwiesen. Vielmehr konnte gezeigt werden, dass die erfolgreiche Expansion CMV-spezifischer T-Zellen mittels Kreuzpr{\"a}sentation von Antigenen MVA-infizierter Leukozyten durch DCs erfolgte. Die Phagozytose von apoptotischen Material von MVA-infizierten Leukozyten mit anschließender Antigenprozessierung induzierte eine vollst{\"a}ndige Ausreifung der DCs in vitro einhergehend mit erh{\"o}hter IL-12-Expression, was erheblich zu einer erfolgreiche T-Zell-Stimulation und -Expansion beitrug. Neben pp65-spezifischen T-Zellen wurden auch IE1-spezifische T-Zellen expandiert, wenn auch in einem geringeren Ausmaß. Der gr{\"o}ßte Teil der expandierten T-Zellen wies einen Effektor-Ged{\"a}chtnis-(EM)-Ph{\"a}notyp auf. Ein kleinerer Anteil besaß jedoch einen zentralen Ged{\"a}chtnis-(CM)-Ph{\"a}notyp, welcher bekannt ist f{\"u}r eine Langzeitpersistenz und eine erfolgreiche Etablierung eines T-Zell-Ged{\"a}chtnis-Pools. Dar{\"u}ber hinaus wurden keine Vaccinia-spezifischen T-Zellen der pockengeimpften Spender expandiert. Wodurch ist die Immunogenit{\"a}t der CMV-Antigene nicht beeintr{\"a}chtigt ist. Die drei untersuchten MVA-CMV-Vakzinkandidaten erf{\"u}llen alle Stabilit{\"a}ts-, Immunogenit{\"a}ts- und Sicherheitsbestimmungen der Europ{\"a}ischen Arzneimittelbeh{\"o}rde (EMEA) f{\"u}r virale Vektorimpfstoffe und sind deshalb bereit f{\"u}r die cGMP-Produktion und anschließende klinische Pr{\"u}fung.}, subject = {Zielzelle }, language = {de} } @article{MaurerSerflingterMeulenetal.1991, author = {Maurer, Bernd and Serfling, Edgar and ter Meulen, Volker and Rethwilm, Axel}, title = {Transcription factor AP-1 modulates the activity of the human foamy virus long terminal repeat}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61444}, year = {1991}, abstract = {The human foamy virus (HFV) contains within the UJ region of its long terminal repeat (L TR) three perfect consensus sequences for the binding of the inducible transcription factor AP-1. Results of DNase I footprint protection and gel retardation assays demonstrated that proteins in extracts of HeLa and BHK-21 cells as weil as bacterially expressed Jun and Fos proteins bind to these AP-1 sites. By conducting transient expression assays using chloramphenicol acetyltransferase plasmids carrying LTR sequences with point-mutated AP-1 sites it was found that the three AP-1 sites contribute to the optimal activity ofthe HFV promoter. It is shown that lnduction of the HFV L TR by 12-O-tetradecanoylphorbol-13-acetate (TPA) and serum factors is mediated through the AP-1 sites.}, subject = {Virologie}, language = {en} } @article{RethwilmMoriMaureretal.1990, author = {Rethwilm, Axel and Mori, Kazuyasu and Maurer, Bernd and ter Meulen, Volker}, title = {Transacting transcriptional activation of human spumaretrovirus LTR in infected cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61488}, year = {1990}, abstract = {The long terminal repeat (LTR) of the human spumaretrovirus (HSRV) was examined with respect to its ability to function as transcriptional promotor in virus-infected and uninfected cells. Transient transfections using a plasmid in which the 3' L TR of HSRV was coupled to the bacterial chloramphenicol cetyltransferase (cat) gene revealed that the Ievei of HSRV LTR-directed cat gene expression was markedly increased in HSRV-infected cells compared to uninfected cells. Northern blot analysis of cat mRNA from transfected cultures suggests that transactivation of HSRVdirected gene expression occurs at the transcriptionallevel.}, subject = {Virologie}, language = {en} } @article{RethwilmErlweinBaunachetal.1991, author = {Rethwilm, Axel and Erlwein, Otto and Baunach, Gerald and Mauerer, Bernd and ter Meulen, Volker}, title = {The transcriptional transactivator of human foamy virus maps to the bel 1 genomic region}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47342}, year = {1991}, abstract = {The human foamy virus (HFV) genome possesses three open reading frames (bel I, 2, and 3) located between env and the 3' long terminal repeat. By analogy to other human retroviruses this region was selected as the most Iikely candidate to encode the viral transactivator. ResuIts presented here confirmed this and showed further that a deletion introduced only into the bell open reading frame of a plasmid derived from an infectious molecular clone of HFV abolished transactivation. In contrast, deletions in bel 2 and bel 3 had only minor effects on the ability to transactivate. The role of the bel I genomic region as a transactivator was further investigated by eukaryotic expression of a genome fragment of HFV spanning the bel I open reading frame. A construct expressing bell under control of a heterologous promoter was found to transactivate the HFV long terminal repeat in a dose-dependent fashion. Furthermore, it is shown that the U3 region of the HFV long terminal repeat is sufficient to respond to the HFV transactivator.}, subject = {Virologie}, language = {en} } @article{GowSimpsonSchliephakeetal.1992, author = {Gow, J. W. and Simpson, K. and Schliephake, Andreas and Behan, W. M. and Morrison, L. J. and Cavanagh, H. and Rethwilm, Axel and Behan, P. O.}, title = {Search for retrovirus in the chronic fatigue syndrome}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61436}, year = {1992}, abstract = {Aim: To examine peripheral blood and skeletal muscle from patients with chronic fadgue syndrome for exogenous retrovirus. Methods: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reacdon (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques. Results: No difference between the padent and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV VII). An endogenous gag band was observed in both the padent and control groups. All sera were negative for antibody to human foamy virus. Conclusion: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.}, subject = {Virologie}, language = {en} } @article{JocherRethwilmKapposetal.1990, author = {Jocher, R. and Rethwilm, Axel and Kappos, L. and ter Meulen, Volker}, title = {Search for retroviral sequences in peripheral blood mononuclear cells and brain tissue of multiple sclerosis patients}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61462}, year = {1990}, abstract = {DNAs from peripheral blood mononuclear cells (PBMCs) of 21 patients with multiple sclerosis (MS), 1 patient with tropical spastic paraparesis (TSP) as well as DNAs from brain and spinal cord of 5 MS cases and 3 controls were examined for human T-cell lymphotropic virus (HTLV)-related sequences by polymerase chain reaction. The primers used were derived from the HTLV-1 gag, env and tax genes. Amplified products were separated on agarase gels, blotted onto nylon membranes and hybridized to specific radiolabelled oligonucleotides. The sensitivity of amplification and hybridization was one copy of target DNA in 10\8^5\) cellular genomes. None of the specimens was positive for HTLV-1 sequences except the TSP probe. These negative data are all the more significant because brain -material from MS patients was used in these studies. Our studies thus fail to support speculations that HTLV-I is involved in the aetiology of multiple sclerosis.}, subject = {Virologie}, language = {en} } @article{SegevRagerZismanIsakovetal.1994, author = {Segev, Y. and Rager-Zisman, B. and Isakov, N. and Schneider-Schaulies, Sibylle and ter Meulen, V. and Udem, S. A. and Segal, S. and Wolfson, M.}, title = {Reversal of measles virus mediated increase of phosphorylating activity in persistently infected mouse neuroblastoma cells by anti measles antibodies}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62362}, year = {1994}, abstract = {No abstract available}, subject = {Virologie}, language = {en} } @article{SchneiderSchauliesLiebertBaczkoetal.1989, author = {Schneider-Schaulies, Sibylle and Liebert, U. G. and Baczko, K. and Cattaneo, R. and Billeter, M. and ter Meulen, V.}, title = {Restriction of measles virus gene expression in acute and subacute encephalitis in Lewis rats}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62266}, year = {1989}, abstract = {No abstract available}, subject = {Virologie}, language = {en} } @article{SchneiderSchauliesLiebertBaczkoetal.1990, author = {Schneider-Schaulies, Sibylle and Liebert, U. G. and Baczko, K. and ter Meulen, V.}, title = {Restricted expression of measles virus in primary rat astroglial cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62283}, year = {1990}, abstract = {No abstract available}, subject = {Virologie}, language = {en} }