@article{AguzziBothAnhauseretal.1992, author = {Aguzzi, A. and Both, K. and Anhauser, I. and Horak, I. and Rethwilm, Axel and Wagner, EF.}, title = {Expression of human foamy virus is differentially regulated during development in transgenic mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-55290}, year = {1992}, abstract = {Tbe human foamy virus (HFV) is a recently characterized member ofthe spumavirus family. Although no diseases have been unequivocally associated with HFV infection, expression of HFV regulatory genes in transgenie mice induces a characteristic aeute neuro degenerative disease and a myopathy. To better eharaeterize the sequenee of events leading to disease, and to gain a better understanding of the underlying pathogenetic meehanisms, we have analyzed in detail the transgene expression pattern during development. Transcription of a construet containing all regulatory elements and aneillary genes of mv was analyzed by in situ hybridization and was shown to occur in two distinct phases. At midgestation, low but widespread expression was first deteeted in eells of extraembryonie tissues. Later, various tissues originating from embryonie mesoderm, neuroeetoderm, and neural erest transeribed the transgene at moderate levels. However, expression deereased dramatically during late gestation and was suppressed shortly after birth. After a latency period of up to 5 weeks, transeription of the transgene resumed in single eelJs distributed irregularly in the central nervous system and in the skeletal museIe. By the age of 8 weeks, an increasing number of eells displayed much higher expression levels than in embryonie Iife and eventually underwent severe degenerative ehanges. These findings demonstrate that HFV transgene expression is differentially regulated in development and that HFV cytotoxicity may be dose-dependent. Such biphasic pattern of expression differs from that of murine retroviruses and may be explained by the specificity of HFV regulatory elements in combination with cellular faetors. Future studies of this model system should, therefore, provide novel insights in the mechanisms controlling retrovirallatency.}, subject = {Virologie}, language = {en} } @article{AvotaGassertSchneiderSchaulies2011, author = {Avota, Elita and Gassert, Evelyn and Schneider-Schaulies, Sibylle}, title = {Cytoskeletal Dynamics: Concepts in Measles Virus Replication and Immunomodulation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69092}, year = {2011}, abstract = {In common with most viruses, measles virus (MV) relies on the integrity of the cytoskeleton of its host cells both with regard to efficient replication in these cells, but also retention of their motility which favors viral dissemination. It is, however, the surface interaction of the viral glycoprotein (gp) complex with receptors present on lymphocytes and dendritic cells (DCs), that signals effective initiation of host cell cytoskeletal dynamics. For DCs, these may act to regulate processes as diverse as viral uptake and sorting, but also the ability of these cells to successfully establish and maintain functional immune synapses (IS) with T cells. In T cells, MV signaling causes actin cytoskeletal paralysis associated with a loss of polarization, adhesion and motility, which has been linked to activation of sphingomyelinases and subsequent accumulation of membrane ceramides. MV modulation of both DC and T cell cytoskeletal dynamics may be important for the understanding of MV immunosuppression at the cellular level.}, subject = {Virologie}, language = {en} } @article{BaunachMaurerHahnetal.1993, author = {Baunach, Gerald and Maurer, Bernd and Hahn, Heidi and Kranz, Manuela and Rethwilm, Axel}, title = {Functional analysis of human foamy virus accessory reading frames}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61398}, year = {1993}, abstract = {No abstract available}, subject = {Virologie}, language = {en} } @book{BockGauchGiernatetal.2013, author = {Bock, Stefanie and Gauch, Fabian and Giernat, Yannik and Hillebrand, Frank and Kozlova, Darja and Linck, Lisa and Moschall, Rebecca and Sauer, Markus and Schenk, Christian and Ulrich, Kristina and Bodem, Jochen}, title = {HIV-1 : Lehrbuch von Studenten f{\"u}r Studenten}, organization = {Bachelor- und Masterkurs Virologie 2013}, isbn = {978-3-923959-90-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78980}, publisher = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Dies ist ein Lehrbuch {\"u}ber die HIV-1 Replikation, Pathogenese und Therapie. Es richtet sich an Studenten der Biologie und der Medizin, die etwas mehr {\"u}ber HIV erfahren wollen und stellt neben virologischen Themen auch die zellul{\"a}ren Grundlagen dar. Es umfasst den Viruseintritt, die reverse Transkription, Genom-Integration, Transkriptionsregualtion, die Kotrolle des Spleißens, der Polyadenylierung und des RNA-Exportes. Die Darstellung wird abgerundet mit Kapiteln zum intrazellul{\"a}rem Transport, zu Nef und zum Virusassembly. In zwei weiteren Kapitel wird die HIV-1 Pathogenese und die Therapie besprochen. Zur Lernkontrolle sind den Kapiteln Fragen und auch Klausurfragen angef{\"u}gt.}, subject = {HIV}, language = {de} } @article{BotheAguzziLassmannetal.1991, author = {Bothe, Katrin and Aguzzi, Adriano and Lassmann, Hans and Rethwilm, Axel and Horak, Ivan}, title = {Progressive encephalopathy and myopathy in transgenic mice expressing human foamy virus genes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61453}, year = {1991}, abstract = {Transgenie mice carrying the bel region of human foamy retrovirus (HFV) under transcriptional control of its own long terminal repeat expressed tbe transgene in their centrat nervous systems and in smootb and striated muscle tissues. The animals developed a progressive degenerative disease of tbe centrat nervous system and of the striated muscle. Because expression of tbe transgene was dosely correlated witb the appearance of structural damage and inflammatory reactions were scanty, the disease is likely to be caused directly by tbe HFV proteins. These unexpected findings call for a reevaluation of tbe patbogenic potential of HFV in humans.}, subject = {Virologie}, language = {en} } @article{BrinkmannSchwinnMuelleretal.1993, author = {Brinkmann, R. and Schwinn, A. and M{\"u}ller, J. and Stahl-Hennig, C. and Coulibaly, C. and Hunsmann, G. and Czub, S. and Rethwilm, Axel and D{\"o}rries, R. and ter Meulen, Volker}, title = {In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61415}, year = {1993}, abstract = {The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIOS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIV\(_{mac25}\), strain as well as the infectious clone (SIV\(_239\)). Infectious viruswas produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue.}, subject = {Virologie}, language = {en} } @article{ErlweinRethwilm1993, author = {Erlwein, Otto and Rethwilm, Axel}, title = {BEL-1 transactivator responsive sequences in the long terminal repeat of human foamy virus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61402}, year = {1993}, 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{FluegelMaurerBannertetal.1987, author = {Fl{\"u}gel, Rolf M. and Maurer, Bernd and Bannert, Helmut and Rethwilm, Axel and Schnitzler, Paul and Darai, Gholamreza}, title = {Nucleotide sequence analysis of a cloned DNA fragment from human cells reveals homology to retrotransposons}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61525}, year = {1987}, abstract = {During molecular cloning of proviral DNA of human. spumaretroVirus, various recombinant clones were estabUshed and analyzed. Blot hybridization revealed that one of the recoinbinant plasmids bad the characteristic features of a member of the long interspersed repetitive sequences famlly. The DNA element was analyzed by restrictioil mapping and nuelootide sequencing. It showed a high degree of amino acid sequence homology of 54.3\% when conipared with the 5'-terminal part of the pol gelie product of the murine retrotransposon LIMd. The 3' region of the cloned DNA element encodes proteins witb an even higher degree of homology of 67.4\% in comparison to the corresponding parts of a member of the primate Kpnl sequence family.}, subject = {Virologie}, language = {en} } @article{FluegelRethwilmMaureretal.1987, author = {Fl{\"u}gel, Rolf M. and Rethwilm, Axel and Maurer, Bernd and Darai, Gholamreza}, title = {Nucleotide sequence analysis of the env gene and its flanking regions of the human spumaretrovirus reveals two novel genes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61509}, year = {1987}, abstract = {Recombinant clonesthat represent the 3' part ofthe genome of the human spumaretrovirus (foamy virus) were established from viral DNA and from DNA complementary to viral RNA. The recombinant clones were characterized by blot hybridizations and nucleotide sequence analysis. The deduced protein sequence of the clones at their 5' ends was found to be homologous to the 3' domain of retroviral reverse transcriptases. Downstream of a small intergerne pol-env region a long open reading frame of 985 amino acid residues was identified that according to its genomic location, size, glycosylation signals, and hydrophobicity protile closely resembles the lentiviral env genes. The spumaretroviral env gene is followed by two open reading frames, termed bel-l and bel-2 which are located between env and the long terminal repeat region. The long terminal repeat of 1259 nucleotides is preceded by a polypurine tract and contains the canonical signal sequences characteristic for transcriptional regulation of retroviruses. The provisional classitication of the spumaretrovirus subfamily is discussed.}, subject = {Virologie}, language = {en} }