@article{LutzHeuerBehlichetal.2013, author = {Lutz, Manfred B. and Heuer, Marion and Behlich, Anna-Sophie and Lee, Ji-Sook and Ribechini, Eliana and Jo, Eun-Kyeong}, title = {The 30-kDa and 38-kDa antigens from Mycobacterium tuberculosis induce partial maturation of human dendritic cells shifting CD4+ T cell responses towards IL-4 production}, series = {BMC Immunology}, journal = {BMC Immunology}, doi = {10.1186/1471-2172-14-48}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96871}, year = {2013}, abstract = {Background Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases. Although 99\% of individuals infected with Mtb develop a CD4+ Th1 and CD8+ T cell mediated immunity as measured by tuberculin skin test, this results only in partial protection and Mtb vaccines are not effective. Deviation of immune responses by pathogens towards a Th2 profile is a common mechanism of immune evasion, typically leading to the persistence of the microbes. Results Here we tested the stimulatory capacity of selective Mtb antigens on human monocyte-derived dendritic cell (DC) maturation and cytokine production. DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers. All Mtb antigens induced variable levels of IL-6 and low levels of IL-10, there was no release of IL-12p70 detectable. Substantial IL-12p40 production was restricted to LPS or H37Ra and H37Rv preparations. Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4+ T cells after secondary stimulation as compared to H37Ra and H37Rv preparations. Conclusion Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.}, language = {en} } @article{SchneiderSchauliesBieringerHanetal.2013, author = {Schneider-Schaulies, J{\"u}rgen and Bieringer, Maria and Han, Jung Woo and Kendl, Sabine and Khosravi, Mojtaba and Plattet, Philippe}, title = {Experimental Adaptation of Wild-Type Canine Distemper Virus (CDV) to the Human Entry Receptor CD150}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0057488}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96537}, year = {2013}, abstract = {Canine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17red adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (102 pfu/ml) in Vero cells expressing human CD150 (Vero-hSLAM). After three passages using these cells virus was adapted to human CD150 and replicated to high titres (105 pfu/ml). Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G) was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.}, language = {en} } @article{BodemSchromMoschalletal.2013, author = {Bodem, Jochen and Schrom, Eva-Maria and Moschall, Rebecca and Hartl, Maximilian J. and Weitner, Helena and Fecher, David and Langemeier, J{\"o}rg and W{\"o}hrl, Brigitta M.}, title = {U1snRNP-mediated suppression of polyadenylation in conjunction with the RNA structure controls poly (A) site selection in foamy viruses}, series = {Retrovirology}, journal = {Retrovirology}, doi = {10.1186/1742-4690-10-55}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96085}, year = {2013}, abstract = {Background During reverse transcription, retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. To express full-length transcripts, retroviruses have to suppress polyadenylation in the 5′LTR and activate polyadenylation in the 3′LTR. Foamy viruses have a unique LTR structure with respect to the location of the major splice donor (MSD), which is located upstream of the polyadenylation signal. Results Here, we describe the mechanisms of foamy viruses regulating polyadenylation. We show that binding of the U1 small nuclear ribonucleoprotein (U1snRNP) to the MSD suppresses polyadenylation at the 5′LTR. In contrast, polyadenylation at the 3′LTR is achieved by adoption of a different RNA structure at the MSD region, which blocks U1snRNP binding and furthers RNA cleavage and subsequent polyadenylation. Conclusion Recently, it was shown that U1snRNP is able to suppress the usage of intronic cryptic polyadenylation sites in the cellular genome. Foamy viruses take advantage of this surveillance mechanism to suppress premature polyadenylation at the 5'end of their RNA. At the 3'end, Foamy viruses use a secondary structure to presumably block access of U1snRNP and thereby activate polyadenylation at the end of the genome. Our data reveal a contribution of U1snRNP to cellular polyadenylation site selection and to the regulation of gene expression.}, subject = {Polyadenylierung}, language = {en} } @article{SchneiderSchauliesLiebertBaczkoetal.1988, author = {Schneider-Schaulies, Sibylle and Liebert, UG and Baczko, K, and ter Meulen, V.}, title = {Molecular Biological Analysis of Measles Virus Gene Expression in the CNS of Acutely and Persistently Infected Rat Brain Cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-81784}, year = {1988}, subject = {Virologie}, language = {en} } @article{SchneiderSchauliesLiebertBaczkoetal.1988, author = {Schneider-Schaulies, Sibylle and Liebert, UG and Baczko, K. and ter Meulen, V.}, title = {Molecular Biological Aspects of Virus-Induced Subacute Encephalomyelitis in Lewis Rats}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-81776}, year = {1988}, abstract = {no abstract available}, subject = {Biologie}, language = {en} } @article{MuellerKrennCzubetal.1993, author = {M{\"u}ller, J. and Krenn, V. and Czub, S. and Schindler, C. and Kneitz, C. and Kerkau, T. and Stahl-Henning, C. and Coulibaly, C. and Hunsmann, G. and Rethwilm, Axel and ter Meulen, Volker and M{\"u}ller-Hermelink, H. K.}, title = {The thymus in SIV infection}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80265}, year = {1993}, abstract = {no abstract available}, subject = {HIV-Infektion}, language = {en} } @article{JacobsBockSchuchetal.2012, author = {Jacobs, Graeme and Bock, Stefanie and Schuch, Anita and Moschall, Rebecca and Schrom, Eva-Maria and Zahn, Juliane and Reuter, Christian and Preiser, Wolfgang and Rethwilm, Axel and Engelbrecht, Susan and Krekau, Thomas and Bodem, Jochen}, title = {Construction of a high titer Infectious HIV-1 subtype C proviral clone from South Africa}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76340}, year = {2012}, abstract = {The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected patients are as high as those from patients with subtype B. Here, we describe the sequencing and construction of a new HIV-1 subtype C proviral clone (pZAC), replicating more than one order of magnitude better than the previous subtype C plasmids. We identify the env-region for being the determinant for the higher viral titers and the pZAC Env to be M-tropic. This higher replication capacity does not lead to a higher cytotoxicity compared to previously described subtype C viruses. In addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails to fully counteract CD317.}, subject = {HIV}, language = {en} } @article{KasangUlmerDonhauseretal.2012, author = {Kasang, Christa and Ulmer, Albrecht and Donhauser, Norbert and Schmidt, Barabara and Stich, August and Klinker, Hartwig and Kalluvya, Samuel and Koutsilieri, Eleni and Rethwilm, Axel and Scheller, Carsten}, title = {HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75100}, year = {2012}, abstract = {Background: HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression. Methods: In an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA. Results: CD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40\% [percentile range 48.76-67.70] versus 73.34\% [65.21-78.92], p = 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70]; p = 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; p = 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26]; p = 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; p = 0.0782). Viral load in both groups was similar (0.8 × 105 ng/ml [0.2-42.4 × 105] vs. 1.1 × 105 [0.5-12.2 × 105]; p = 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone. Conclusions: Patients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.}, subject = {HIV}, language = {en} } @article{LangenhorstGogishviliRibechinietal.2012, author = {Langenhorst, Daniela and Gogishvili, Tea and Ribechini, Eliana and Kneitz, Susanne and McPherson, Kirsty and Lutz, Manfred B. and H{\"u}nig, Thomas}, title = {Sequential induction of effector function, tissue migration and cell death during polyclonal activation of mouse regulatory T-cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76009}, year = {2012}, abstract = {The ability of CD4+Foxp3+ regulatory T-cells (Treg) to produce interleukin (IL)-10 is important for the limitation of inflammation at environmental interfaces like colon or lung. Under steady state conditions, however, few Tregs produce IL-10 ex vivo. To investigate the origin and fate of IL-10 producing Tregs we used a superagonistic mouse anti-mouse CD28 mAb (CD28SA) for polyclonal in vivo stimulation of Tregs, which not only led to their numeric expansion but also to a dramatic increase in IL-10 production. IL-10 secreting Tregs strongly upregulated surface receptors associated with suppressive function as compared to non-producing Tregs. Furthermore, polyclonally expanding Tregs shifted their migration receptor pattern after activation from a CCR7+CCR52 lymph node-seeking to a CCR72CCR5+ inflammationseeking phenotype, explaining the preferential recruitment of IL-10 producers to sites of ongoing immune responses. Finally, we observed that IL-10 producing Tregs from CD28SA stimulated mice were more apoptosis-prone in vitro than their IL-10 negative counterparts. These findings support a model where prolonged activation of Tregs results in terminal differentiation towards an IL-10 producing effector phenotype associated with a limited lifespan, implicating built-in termination of immunosuppression.}, subject = {Medizin}, language = {en} } @article{Lutz2012, author = {Lutz, Manfred B.}, title = {Therapeutic Potential of Semi-Mature Dendritic Cells for Tolerance Induction}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75535}, year = {2012}, abstract = {Dendritic cells (DCs) are major players in the control of adaptive tolerance and immunity. Therefore, their specific generation and adoptive transfer into patients or their in vivo targeting is attractive for clinical applications. While injections of mature immunogenic DCs are tested in clinical trials, tolerogenic DCs still are awaiting this step. Besides the tolerogenic potential of immature DCs, also semi-mature DCs can show tolerogenic activity but both types also bear unfavorable features. Optimal tolerogenic DCs, their molecular tool bar, and their use for specific diseases still have to be defined. Here, the usefulness of in vitro generated and adoptively transferred semi-mature DCs for tolerance induction is outlined. The in vivo targeting of semi-mature DCs as represented by steady state migratory DCs are discussed for treatment of autoimmune diseases and allergies. First clinical trials with transcutaneous allergen application may point to their therapeutic use in the future.}, subject = {Medizin}, language = {en} } @article{SpannausHartlWoehrletal.2012, author = {Spannaus, Ralf and Hartl, Maximilian J. and W{\"o}hrl, Birgitta M. and Rethwilm, Axel and Bodem, Jochen}, title = {The prototype foamy virus protease is active independently of the integrase domain}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75370}, year = {2012}, abstract = {Background: Recently, contradictory results on foamy virus protease activity were published. While our own results indicated that protease activity is regulated by the viral RNA, others suggested that the integrase is involved in the regulation of the protease. Results: To solve this discrepancy we performed additional experiments showing that the protease-reverse transcriptase (PR-RT) exhibits protease activity in vitro and in vivo, which is independent of the integrase domain. In contrast, Pol incorporation, and therefore PR activity in the viral context, is dependent on the integrase domain. To further analyse the regulation of the protease, we incorporated Pol in viruses by expressing a GagPol fusion protein, which supported near wild-type like infectivity. A GagPR-RT fusion, lacking the integrase domain, also resulted in wild-type like Gag processing, indicating that the integrase is dispensable for viral Gag maturation. Furthermore, we demonstrate with a trans-complementation assays that the PR in the context of the PR-RT protein supports in trans both, viral maturation and infectivity. Conclusion: We provide evidence that the FV integrase is required for Pol encapsidation and that the FV PR activity is integrase independent. We show that an active PR can be encapsidated in trans as a GagPR-RT fusion protein.}, subject = {Medizin}, 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{SchneiderSchauliesHuenigSchimpletal.1986, author = {Schneider-Schaulies, J{\"u}rgen and H{\"u}nig, T. and Schimpl, A. and Wecker, E.}, title = {Kinetics of cellular oncogene expression in mouse lymphocytes ; I. Expression of c-myc and c-ras Ha in T lymphocytes induced by various mitogens}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54803}, year = {1986}, abstract = {Murine spienie T lymphocytes display maximal cellular myc gene (c-myc) expression already 3 h after concanavalin A timulation and sub equent down-regulation before the onset of DNA syntbesis. Stimulation by leucoagglulinin in the prcsence or absence of interleukin 2 Ieads to only low initiaJ Ievels of c-myc-specific RNA which, however, increase later on. A similar pattero of c-myc expression is shown by the Lyt- 2+ T cell subpopulation stimuiated with eilher concanavalin A or leucoagglutinin in the prescncc of interleukin 2. Although eH]thyn1idine incorporation was identical, the leucoagglutinin-stimulated Lyt-2+ T cells werc void of any demon. trable c-mycspeci. fic RNA at 3 h post-stimulation. Thus, the kinetics of c-myc expression in mause T lymphocytes arenot at all uniform, but depend on the mitogen and the subpopulation. [n contrast, lcvel8 of c-rasH•-spccific R A wcre always low at early times, always increased towards tbe onset ofDNA synthesis and down-regulationwas not observed.}, subject = {Immunologie}, language = {en} } @article{OberlaenderPletinckxDaehleretal.2011, author = {Oberl{\"a}nder, Uwe and Pletinckx, Katrien and D{\"a}hler, Anja and M{\"u}ller, Nora and Lutz, Manfred and Arzberger, Thomas and Riederer, Peter and Gerlach, Manfred and Koutsilieri, Eleni and Scheller, Carsten}, title = {Neuromelanin is an Immune Stimulator for Dendritic Cells in vitro}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69210}, year = {2011}, abstract = {Background: Parkinson's disease (PD) is characterized at the cellular level by a destruction of neuromelanin (NM)-containing dopaminergic cells and a profound reduction in striatal dopamine. It has been shown recently that antimelanin antibodies are increased in sera of Parkinson patients, suggesting that NM may act as an autoantigen. In this study we tested whether NM is being recognized by dendritic cells (DCs), the major cell type for inducing Tand B-cell responses in vivo. This recognition of NM by DCs is a prerequisite to trigger an adaptive autoimmune response directed against NM-associated structures. Results: Murine DCs were treated with NM of substantia nigra (SN) from human subjects or with synthetic dopamine melanin (DAM). DCs effectively phagocytized NM and subsequently developed a mature phenotype (CD86high/MHCIIhigh). NM-activated DCs secreted the proinflammatory cytokines IL-6 and TNF-a. In addition, they potently triggered T cell proliferation in a mixed lymphocyte reaction, showing that DC activation was functional to induce a primary T cell response. In contrast, DAM, which lacks the protein and lipid components of NM but mimics the dopamine-melanin backbone of NM, had only very little effect on DC phenotype and function. Conclusions: NM is recognized by DCs in vitro and triggers their maturation. If operative in vivo, this would allow the DC-mediated transport and presentation of SN antigens to the adaptive immune system, leading to autoimmmunity in susceptible individuals. Our data provide a rationale for an autoimmune-based pathomechanism of PD with NM as the initial trigger.}, subject = {Immunstimulation}, language = {en} } @article{AvotaGulbinsSchneiderSchaulies2011, author = {Avota, Elita and Gulbins, Erich and Schneider-Schaulies, Sibylle}, title = {DC-SIGN Mediated Sphingomyelinase-Activation and Ceramide Generation Is Essential for Enhancement of Viral Uptake in Dendritic Cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69056}, year = {2011}, abstract = {As pattern recognition receptor on dendritic cells (DCs), DC-SIGN binds carbohydrate structures on its pathogen ligands and essentially determines host pathogen interactions because it both skews T cell responses and enhances pathogen uptake for cis infection and/or T cell trans-infection. How these processes are initiated at the plasma membrane level is poorly understood. We now show that DC-SIGN ligation on DCs by antibodies, mannan or measles virus (MV) causes rapid activation of neutral and acid sphingomyelinases followed by accumulation of ceramides in the outer membrane leaflet. SMase activation is important in promoting DC-SIGN signaling, but also for enhancement of MV uptake into DCs. DCSIGN-dependent SMase activation induces efficient, transient recruitment of CD150, which functions both as MV uptake receptor and microbial sensor, from an intracellular Lamp-1+ storage compartment shared with acid sphingomyelinase (ASM) within a few minutes. Subsequently, CD150 is displayed at the cell surface and co-clusters with DC-SIGN. Thus, DCSIGN ligation initiates SMase-dependent formation of ceramide-enriched membrane microdomains which promote vertical segregation of CD150 from intracellular storage compartments along with ASM. Given the ability to promote receptor and signalosome co-segration into (or exclusion from) ceramide enriched microdomains which provide a favorable environment for membrane fusion, DC-SIGN-dependent SMase activation may be of general importance for modes and efficiency of pathogen uptake into DCs, and their routing to specific compartments, but also for modulating T cell responses.}, subject = {Dendritische Zelle}, language = {en} } @article{KasangKalluvyaMajingeetal.2011, author = {Kasang, Christa and Kalluvya, Samuel and Majinge, Charles and Stich, August and Bodem, Jochen and Kongola, Gilbert and Jacobs, Graeme B. and Mllewa, Mathias and Mildner, Miriam and Hensel, Irina and Horn, Anne and Preiser, Wolfgang and van Zyl, Gert and Klinker, Hartwig and Koutsilieri, Eleni and Rethwilm, Axel and Scheller, Carsten and Weissbrich, Benedikt}, title = {HIV drug resistance (HIVDR) in antiretroviral therapy-naive patients in Tanzania not eligible for WHO threshold HIVDR survey is dramatically high}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69024}, year = {2011}, abstract = {Background: The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5\%. In this study we investigated whether the rate of HIVDR in patients ,25 years is representative for HIVDR in the rest of the therapy-naive population. Methods and Findings: HIVDR was determined in 88 sequentially enrolled ART-naive patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged, 25 years and 68 patients were aged 25-63 years. The frequency of HIVDR in the study population was 14.8\% (95\%; CI 0.072-0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients .25 years had a significantly higher HIVDR frequency than younger patients (19.1\%; 95\% CI 0.095-0.28) versus 0\%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma. Conclusions: ART-naive patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naive population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naive HIV-infected population.}, subject = {Tansania}, language = {en} } @article{SchneiderSchauliesSchneiderSchauliesSchusteretal.1994, author = {Schneider-Schaulies, Sibylle and Schneider-Schaulies, J{\"u}rgen and Schuster, A. and Bayer, M. and Pavlovic, J. and ter Meulen, V.}, title = {Cell type specific MxA-mediated inhibition of measles virus transcription in human brain cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62255}, year = {1994}, abstract = {No abstract available}, 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{SchnorrSchneiderSchauliesSimonJoedickeetal.1993, author = {Schnorr, J. J. and Schneider-Schaulies, Sibylle and Simon-J{\"o}dicke, A. and Pavlovic, J. and Horisberger, M. A. and ter Meulen, V.}, title = {MxA dependent inhibition of Measles Virus glycoprotein synthesis in a stably transfected human monocytic cell line}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62353}, year = {1993}, abstract = {No abstract available}, subject = {Virologie}, language = {en} } @article{SchneiderSchauliesLiebertRagerZismanetal.1992, author = {Schneider-Schaulies, Sibylle and Liebert, U. G. and Rager-Zisman, B. and Wolfson, M. and ter Meulen, V.}, title = {Antibody-dependent transcriptional regulation of measles virus in persistently infected neural cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62329}, year = {1992}, abstract = {No abstract available}, subject = {Virologie}, language = {en} } @article{KrausSchneiderSchauliesMiyasakaetal.1991, author = {Kraus, E. and Schneider-Schaulies, Sibylle and Miyasaka, M. and Tamatani, T. and Sedgwick, J.}, title = {Augmentation of major histocompatibility complex class I and ICAM-1 expression on glial cells following measles virus infection: evidence for the role of type-1 interferon}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62301}, year = {1991}, abstract = {No abstract available}, subject = {Virologie}, language = {en} } @article{SchneiderSchauliesKrethHofmannetal.1991, author = {Schneider-Schaulies, Sibylle and Kreth, H. W. and Hofmann, G. and Billeter, M. A. and ter Meulen, V.}, title = {Expression of measles virus RNA in peripheral blood mononuclear cells of patients with measles, SSPE, and autoimmune diseases}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62297}, year = {1991}, 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} } @article{LiebertSchneiderSchauliesBaczkoetal.1990, author = {Liebert, U. G. and Schneider-Schaulies, Sibylle and Baczko, K. and ter Meulen, V.}, title = {Antibody-induced restriction of viral gene expression in measles encephalitis in rats}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62271}, year = {1990}, 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{SchneiderSchauliesSchneiderSchauliesSchusteretal.1994, author = {Schneider-Schaulies, J{\"u}rgen and Schneider-Schaulies, S. and Schuster, A. and Bayer, M. and Pavlovic, J. and ter Meulen, V.}, title = {Cell type specific MxA-mediated inhibition of measles virus transcription in human brain cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-34313}, year = {1994}, abstract = {Measles virus (MV)-specific transcription in human brain cells is characterized by particularly low abundances of the distal mRNAs encoding the MV envelope proteins. Similar transcriptional restrictions of the closely related vesicular stomatitis virus have been observed in mouse fibroblasts constitutively expressing the interferon-inducible MxA protein (P. Staeheli and J. Pavlovic, J. Virol. 65:4498-4501, 1991). We found that MV infection of human brain cells is accompanied by rapid induction and high-level expression of endogenous MxA proteins. After stable transfection of MxA, human glioblastoma cells (U-87-MxA) released 50- to 100-fold less infectious virus and expression of viral proteinswas highly restricted. The overall MV-specific transcription Ievels were reduced by up to 90\%, accompanied by low relative frequencies of the distal MV-specific mRNAs. These restrictions were linked to an inhibition of viral RNA synthesis and not to a decreased stability of the viral RNAs. Our results indicate that expression of MxA is associated with transcriptional attenuation of MV in brain cells, thus probably contributing to the establishment of persistent MV central nervous system infections. In addition, the mechanism of MxA-dependent resistance against MV infection, in contrast to that of vesicular Stomatitis virus, is cell type specific, because an inhibition of MV glycoprotein synthesis independent of transcriptional alterations was observed in MxA-transfected human monocytes}, language = {en} } @article{MaisnerSchneiderSchauliesLiszewskietal.1994, author = {Maisner, A. and Schneider-Schaulies, J{\"u}rgen and Liszewski, M.K. and Atkinson, J.P. and Herrler, G.}, title = {Binding of measles virus to membrane cofactor protein (CD46): importance of disulfide bonds and N-glycans for the receptor function}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-34324}, year = {1994}, abstract = {Two cellular proteins, membrane cofactor protein (MCP) and moesin, were reported recently to be functionally associated with the initiation of a measles virus infection. We bave analyzed the interaction of measles virus with cell surface proteins, using an overlay binding assay with cellular proteins immobilized on nitrocellulose. Among surface-biotinylated proteins from a human rectal tumor cellline (HRT), measles virus, was able to bind only to a 67-kDa proteinthat was identified as MCP. The virus recognized dift'erent isoforms of MCP expressed from human (HRT and HeLa) and simian (Vero) celllines. The binding of measles virus to MCP was abolished after cleavage of the disulfide bonds by reducing agents as weil as after enzymatic release of N-linked oligosaccharides. By contrast, removal of sialic acid or 0-linked oligosaccharides did not aft'ect the recognition of MCP by measles virus. These data indicate that the receptor determinant of MCP is dependent on a conformation of the protein that is maintained by disulfide bonds and N-glycans present in tbe complement binding domains. Our results are consistent with a roJe of MCP as primary attacbment site for measles virus in the initial stage of an infection. The functional relationship between MCP and moesin in a measles virus infection is discussed.}, language = {en} } @article{SchneiderSchauliesSchnorrDunsteretal.1994, author = {Schneider-Schaulies, Sibylle and Schnorr, J.-J. and Dunster, L. M. and Schneider-Schaulies, J{\"u}rgen and ter Meulen, Volker}, title = {The role of host factors in measles virus persistence}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54944}, year = {1994}, abstract = {As critical steps in the life cycle oJ measles virus (Mfl), the e.fficiency of uptake into and replication in susceptible host cells are governed by cellular determinants. Measles virus infections of cells of the human CNS are characterized by particular constraints imposed on v1:ral transcription and translation attenuating viral gene Junctions and thus contributing to the pathogenesis oJ MV persistence in these cells.}, subject = {Immunologie}, language = {en} } @article{DunsterSchneiderSchauliesLoeffleretal.1994, author = {Dunster, L.M. and Schneider-Schaulies, J{\"u}rgen and L{\"o}ffler, S. and Lankes, W. and Schwartz-Albiez, R. and Lottspeich, F. and ter Meulen, V.}, title = {Moesin: a cell membrane protein linked with susceptibility to measles virus infection}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54931}, year = {1994}, abstract = {Measles virus is a highly contagious virus causing acute and persistent diseases in man, the receptor of which is still not weil characterized. We have isolated a monoclonal antibody (mAb), designated mAb 119, which specifically inhibits measles virus infection of susceptible celllines in a dosa-dependent manner. This antibody precipitates a protein with an apparent molecular mass of 75 kDa from 1251 surface-labeled cells and its epitope is present on human peripheral blood mononuclear cells, human celllines, and the African green monkey cellline Vero. Affinity chromatography of detergent-solubilized cell membrane proteins over a Sepharose column with covalently bound mAb 119 led to the partial purification of the 75-kOa protein. Preincubation of measles virus with this affinity-purified protein inhibited measles virus infection dose dependently. Aminoacid microseq,uencing of this protein revealed its identity with the human membrane-organizing extension spike protein moesin, a protein intra- and extracellularly associated with the plasma membrane of cells. Subsequently, an antibody raised against purified moesin (mAb 38/87) was also found to specifically inhibit measles virus infection of susceptible cells and confirmed our data obtained with mAb 119. Our data suggest that moesin is acting as a receptor for measles virus.}, subject = {Immunologie}, language = {en} } @article{ProbstmeierBilzSchneiderSchaulies1994, author = {Probstmeier, R. and Bilz, A. and Schneider-Schaulies, J{\"u}rger}, title = {Expression of the neural cell adhesion molecule and polysialic acid during early mouse embryogenesis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54921}, year = {1994}, abstract = {The expression of the neural cell adhesion molccule (N-CAM) and a 2-8 linked polysialic acid (PSA), whieh is believed to be predominantly expressed on N-CAM, was investigated during early embryonie development ofthe mouse (embryonic days 7.5 to 10.0). By immunoeytoehemistry, in tissue sections, N-CAM and PSA were not detectable at embryonie day 7.5 but were expressed in the prominent body regions such as somites, unsegmented mesoderm, developing heart, and neuroectoderm at embryonie day 8.0 N-CAM and PSA immunoreaetivities were always predominantly associated with tbe plasma membrane. No tissue could be detected which was positive for PSA but negative for N-CAM. In Western blot analysis of whole embryos, by contrast, only the lightly sialylated and PSA-negative 180 and 140 kD isoforms of N-CAM werc present at embryonie day 8.0 and strong expression of PSA-bearing, heavily sialylated N-CAM was not detectable before embryonie day 10.0. In Western blot analysis of N-CAM immunoaffinity purifled from whole embryos and digested with neuraminidase as weil as in Northern blot analysis, the 120 kD isoform of N-CAM or its eorresponding mRN A were not expressed in detectable amounts during the time period investigated.}, subject = {Immunologie}, language = {en} } @article{SchneiderSchauliesSchneiderSchauliesBayeretal.1993, author = {Schneider-Schaulies, Sibylle and Schneider-Schaulies, J{\"u}rgen and Bayer, M. and L{\"o}ffler, S. and ter Meulen, V.}, title = {Spontaneous and differentiation dependent regulation of measles virus gene expression in human glial cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54913}, year = {1993}, abstract = {The expression of measles virus (MV) in six different permanent human glioma cell lines (D-54, U-251, U-138, U-105, U-373, and D-32) was analyzed. Although all celllines were permissive for productive replication of all MV strains tested, U-251, D-54, and D-32 cells spontaneously revealed restrictions of MV transcription similar to those observed for primary rat astroglial cells and brain tissue. In vitro differentiation of D-54 and U-251 cells by substances affecting tbe intracellular cyclic AMP Ievel caused a significant reduction of tbe expression of tbe viral proteins after 18, 72, and 144 b of infection. This pronounced restriction was not paralleled to a comparable Ievel by an inhibition of tbe syntbesis and biological activity in vitro of virus·specific mRNAs as sbown by quantitative Northem (RNA) blot analyses and in vitro translation. The block in viral protein syntbesis could not be attributed to tbe induction of type I interferon by any of tbe substances tested. Our findings indicate tbat down-regulation of MV gene expression in human brain cells can occur by a cell type-rlependent regulation of tbe viral mRNA transcription and a differentiation-dependent regulation of translation, botb of wbicb may be crucial for the establisbment of persistent MV infections in tbe centrat nervous system.}, subject = {Immunologie}, language = {en} } @article{SchneiderSchauliesSchneiderSchauliesterMeulen1993, author = {Schneider-Schaulies, J{\"u}rgen and Schneider-Schaulies, S. and ter Meulen, Volker}, title = {Differential induction of cytokines after primary and persistent measles virus infections of human glial cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54907}, year = {1993}, abstract = {The effect of measles virus (MV) infection on mRNA expression and protein synthesis of cytokines in human malignant glioma celllines (0-54 and U-251) was investigated. Primary MV infections led in both celllines to the induction of interleukin-1 fJ (ll-1 (3), interleukin-6 (IL-6), interferon-(3 (IFN-fJ), and tumor necrosis factor-a (TNF-a). ln contrast, persistently infected astrocytoma lines continually produced IL-6 (two out of 12 lines high Ievels) and IFN-ß, whereas only 1 out of 121ines synthesized TNF-a and none IL-1ß. The pathways for induction of IL-1fJ and TNF-a expression were not suppressed by the persistent MV infection, since IL-1ß and TNF-a could be induced by external stimuli Jike diacylglycerol analog plus calcium ionophore. lnterestingly, persistently infected astrocytoma cells synthesized considerably higher Ievels of ll-1ß and TNF-a than uninfected cells afteradditional external induction. These results suggest that in the centrat nervous system (CNS) of SSPE patients a percentage of persistently infected astrocytes may continually synthesize IL-6 and IFN-ß, and in the presence of additional external stimuli, as possibly provided by activated lymphocytes, might ovarexpress the inflammatory cytokines IL-1 ß and TNF-a. This may be of pathogenetic significance in CNS diseases associated with persistent MV infections.}, subject = {Immunologie}, language = {en} } @article{ArchelosRoggenbuckSchneiderSchauliesetal.1993, author = {Archelos, J. J. and Roggenbuck, K. and Schneider-Schaulies, J{\"u}rgen and Toyka, K. V. and Hartung, H. P.}, title = {Detection and quantification of antibodies to the extracellular domain of Po during experimental allergic neuritis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54896}, year = {1993}, abstract = {Quantification of the peripheral nerve myelin glycoprotein PO and antibodies to PO is difficult due to insolubility of PO in physiological solutions. We have overcome this problern by using the water-soluble recombinant form of the extracellular domain of PO (PO-ED) and describe newly developed assays which allow detection and quantitation of PO and antibodies to PO, in serum and cerebraspinal fluid (CSF). These sensitive and specific assays based on the ELISA technique were used to study humoral immune responses to PO during experimental autoimmune ("allergic") neuritis (EAN). In order to establish these tests, monoclonal antiborlies to different epitopes of rodent and human PO-ED were produced. A two-antibody sandwich-ELISA allowing quantitation of PO Oower detection Iimit of 0.5 ngjml or 30 fmoljml) and an antibody-capture ELISA (lower detection Iimit 1 ng specific antibody jml) to detect antiborlies to PO in serum and CSF were developed. EAN was induced in rats by active immunization with bovine myelin or the neuritogenic protein P2 or by adoptive transfer using P2 specific CD4 positive T cells. Serum and CSF were assayed for the presence of PO-ED and antibodies to PO-ED or P2. Antibodies to PO-ED were detected during active myelin-induced EAN, but not during P2-induced or adaptive transfer EAN. The anti-PO-ED antibodies in the CSF showed a correJation with disease activity. In contrast, in the same model antibodies to P2 persisted long after the disease ceased. No soluble PO-Iike fragments could be found in serum or CSF during any of the three types of EAN. We conclude that PO may be a B-eeil epitope in EAN. These findings warrant a screen for antibodies to PO-ED in human immune neuropathies.}, subject = {Immunologie}, language = {en} } @article{SchneiderSchauliesSchneiderSchauliesBrinkmannetal.1992, author = {Schneider-Schaulies, J{\"u}rgen and Schneider-Schaulies, Sibylle and Brinkmann, R. and Tas, P. and Halbr{\"u}gge, M. and Walter, U. and Holmes, H.C. and ter Meulen, Volker}, title = {HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54872}, year = {1992}, abstract = {Human immunodeficiency virus (HIV-1) infection in the human brain Ieads to characteristic neuropathological changes, which may result indirectly from interactions of the envelope glycoprotein gp 120 with neurons and/or glial cells. We therefore investigated the binding of recombinant gp120 (rgp120) to human neural cells and its effect on int~acellular.s.ignallin~. Herewe pre~ent evidence that rgp120, besides binding to galactocerebroside or galactosyl-sulfatlde, spec1f1cally bmds to a protem receptor of a relative molecular mass of approximately 180,000 Da (180 kDa) pre~ent. on the CD4-negative glioma cells D-54, but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rap1dly 1nduced a tyrosine-specific protein kinase activity leading to tyrosine phosphorylation of 130- and 115-kDa p~oteins. The c~ncentration of intracellular calciumwas not affected by rgp120 in these cells. Our data suggest a novel Signal transduc1ng HIV-1 gp120 receptor on CD4-negative glial cells, which may contribute to the neuropathological changes observed in HIV-1-infected brains.}, subject = {Immunologie}, language = {en} } @article{JaffeyChanShaoetal.1992, author = {Jaffey, P. and Chan, L.-N. L. and Shao, J. and Schneider-Schaulies, J{\"u}rgen and Chan, T.-S.}, title = {Retinoic acid inhibition of serum-induced c-fos transcription in a fibrosarcoma cell line}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54863}, year = {1992}, abstract = {No abstract available}, subject = {Immunologie}, language = {en} } @article{SchneiderSchauliesvonBrunnSchachner1990, author = {Schneider-Schaulies, J{\"u}rgen and von Brunn, A. and Schachner, M.}, title = {Recombinant peripheral myelin protein P\(_o\) confers both adhesion and neurite outgrowth promoting properties}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54841}, year = {1990}, abstract = {To probe into the functional properties of the major peripheral myelin cell surface glycoprotein P 0 , its ability to confer adhesion and neurite outgrowth-promoting properfies was studied in cell culture. Tothis aim, Po was expressed as integral membrane glycoprotein at the surface of CV -1 cells with the help of a recombinant vaccinia virus expression system. Furthermore, the immunoglobulin-like extracellular domain of P0 (P0 -ED) was expressed as soluble profein in a bacterial expression system and used as substrafe coated to plastic dishes or as competitor in cell adhesion and neurite outgrowth-promoting assays. The adhesion of P0 -expressing CV-1 cells to P0 -ED substrafe was specifically inhibitable by polyclonal Po antibodies (54\% :t 6\% ). In addition, the specific interaction between Po molecules could be reduced ( 49\% ± 8\%) by adding soluble P0 -ED to the culture medium, demonstrating that the homophilic inter~ction between recombinant Po molecules can be mediated, at least on one partner of interacting molecules, by the unglycosylated Ig-like domain. Substrate-coated p -ED also conferred adhesion and neurite outgrowth ability to dorsal root ganglion neurons with neurites of a mean length of about 150 ,_..m. This neurite outgrowth was specifically inhibitable by soluble P" (74\% ± 14\%) and P 0 antibodies (65\% ± 9\% ). These observations indicate that Po is capable of displaying two different types of functional roles in the myelination process of . peripheral nerves: The heterophilic interaction with neurons may be responsible for the recognition between axon and myelinating Schwann cell at the onset of myelination, whereas the homophilic interacton may indicate its roJe in the selfrecognition of the apposing loops of Schwann cell surface membranes during the myelination process and in the mature compact myelin sheath.}, subject = {Immunologie}, language = {en} } @article{SchneiderSchauliesSchimplWecker1987, author = {Schneider-Schaulies, J{\"u}rgen and Schimpl, A. and Wecker, E.}, title = {Kinetics of cellular oncogene expression in mouse lymphocytes II. Regulation of c-fos and c-myc gene expression}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54823}, year = {1987}, abstract = {Newly isolated lymphocytes from mousespleensexpress the c-fos oncogene even in the absence of mitogen with maximal mRNA levels 60 min post preparation of single cell suspension, whereas c-myc mRNA Ievels increase only after mitogenic Stimulation with maximal mRNA Ievels 6 h post Stimulation. The half-lives of c-fos mRNA are generally very short; they increase from 14 min (after 30 min of culture) to 70 min (after 2 h of culture). The half-lives of c-myc mRNA decrease from 50 min (at 2 and 6 h post stimulation with concanavalin A) to 12 min (at 48 h post stimulation). The c-fos gene transcription is already tumed on in time-0 lymphocytes 10 min after disruption of the organ structure of the spleens and is down-regulated after 2 h and later. In nuclear run-on experiments with nonstimulated lymphocytes there is already significant transcription of the first exon of c-myc, but almost no elongation of the transcript to exon 2 and 3. In concanavalin A-treated lymphocytes elongation is stimulated about 5-fold within 6 h and returns to background levels at 48 h post Stimulation. · The nuclear run-on analyses of nonactivated lymphocytes showed a signal for RNA complementary to c-myc mRNA detected with a probe specific for the exon 1/intron 1 boundary of c-myc, which disappeared with increasing time of concanavalin A Stimulation. This anti-sense transcription may play a role in regulating the elongation of cmyc transcripts.}, subject = {Lymphozyt}, language = {en} } @article{MonzonCasanovaSteinigerSchweigleetal.2010, author = {Monzon-Casanova, Elisa and Steiniger, Birte and Schweigle, Stefanie and Clemen, Holger and Zdzieblo, Daniela and Starick, Lisa and Mueller, Ingrid and Wang, Chyung-Ru and Rhost, Sara and Cardell, Susanna and Pyz, Elwira and Herrmann, Thomas}, title = {CD1d Expression in Paneth Cells and Rat Exocrine Pancreas Revealed by Novel Monoclonal Antibodies Which Differentially Affect NKT Cell Activation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68477}, year = {2010}, abstract = {Background: CD1d is a nonpolymorphic MHC class I-like molecule which presents nonpeptide ligands, e.g. glycolipids, to NKT cells. These cells are known to have multiple effects on innate and adaptive immune responses and on the development of pathological conditions. In order to analyze CD1d expression and function in the rat, the first rat CD1dspecific monoclonal antibodies (mAbs) were generated. Methodology/Principal Findings: Two mAbs, WTH-1 and WTH-2, were generated which bound equally well to cell surfaceexpressed rat and mouse CD1d. Their non-overlapping epitopes were mapped to the CD1d heavy chain. Flow cytometry and immunohistological analyses revealed a nearly identical degree and pattern of CD1d expression for hematopoieitic cells of both species. Notable is also the detection of CD1d protein in mouse and rat Paneth cells as well as the extremely high CD1d expression in acinar exocrine cells of the rat pancreas and the expression of CD4 on rat marginal zone B cells. Both mAbs blocked a-galactosylceramide recognition by primary rat and mouse NKT cells. Interestingly, the two mAbs differed in their impact on the activation of various autoreactive T cell hybridomas, including the XV19.2 hybridoma whose activation was enhanced by the WTH-1 mAb. Conclusions/Significance: The two novel monoclonal antibodies described in this study, allowed the analysis of CD1d expression and CD1d-restricted T cell responses in the rat for the first time. Moreover, they provided new insights into mechanisms of CD1d-restricted antigen recognition. While CD1d expression by hematopoietic cells of mice and rats was extremely similar, CD1d protein was detected at not yet described sites of non-lymphatic tissues such as the rat exocrine pancreas and Paneth cells. The latter is of special relevance given the recently reported defects of Paneth cells in CD1d2/2 mice, which resulted in an altered composition of the gut flora.}, subject = {Krebs }, language = {en} } @article{BrandlOrtlerHerrmannetal.2010, author = {Brandl, Carolin and Ortler, Sonja and Herrmann, Thomas and Cardell, Susanna and Lutz, Manfred B. and Wiendl, Heinz}, title = {B7-H1-Deficiency Enhances the Potential of Tolerogenic Dendritic Cells by Activating CD1d-Restricted Type II NKT Cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68457}, year = {2010}, abstract = {Background: Dendritic cells (DC) can act tolerogenic at a semi-mature stage by induction of protective CD4+ T cell and NKT cell responses. Methodology/Principal Findings: Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semimature DC that were generated from bone marrow (BM) cells of B7-H12/2 mice and applied to the model of Experimental Autoimmune Encephalomyelitis (EAE). Injections of B7-H1-deficient DC showed increased EAE protection as compared to wild type (WT)-DC. Injections of B7-H12/2 TNF-DC induced higher release of peptide-specific IL-10 and IL-13 after restimulation in vitro together with elevated serum cytokines IL-4 and IL-13 produced by NKT cells, and reduced IL-17 and IFN-c production in the CNS. Experiments in CD1d2/2 and Ja2812/2 mice as well as with type I and II NKT cell lines indicated that only type II NKT cells but not type I NKT cells (invariant NKT cells) could be stimulated by an endogenous CD1d-ligand on DC and were responsible for the increased serum cytokine production in the absence of B7-H1. Conclusions/Significance: Together, our data indicate that BM-DC express an endogenous CD1d ligand and B7-H1 to ihibit type II but not type I NKT cells. In the absence of B7-H1 on these DC their tolerogenic potential to stimulate tolerogenic CD4+ and NKT cell responses is enhanced.}, subject = {Dendritische Zelle}, language = {en} } @article{HerpinBraaschKraeusslingetal.2010, author = {Herpin, Amaury and Braasch, Ingo and Kraeussling, Michael and Schmidt, Cornelia and Thoma, Eva C. and Nakamura, Shuhei and Tanaka, Minoru and Schartl, Manfred}, title = {Transcriptional Rewiring of the Sex Determining dmrt1 Gene Duplicate by Transposable Elements}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68437}, year = {2010}, abstract = {Control and coordination of eukaryotic gene expression rely on transcriptional and posttranscriptional regulatory networks. Evolutionary innovations and adaptations often require rapid changes of such networks. It has long been hypothesized that transposable elements (TE) might contribute to the rewiring of regulatory interactions. More recently it emerged that TEs might bring in ready-to-use transcription factor binding sites to create alterations to the promoters by which they were captured. A process where the gene regulatory architecture is of remarkable plasticity is sex determination. While the more downstream components of the sex determination cascades are evolutionary conserved, the master regulators can switch between groups of organisms even on the interspecies level or between populations. In the medaka fish (Oryzias latipes) a duplicated copy of dmrt1, designated dmrt1bY or DMY, on the Y chromosome was shown to be the master regulator of male development, similar to Sry in mammals. We found that the dmrt1bY gene has acquired a new feedback downregulation of its expression. Additionally, the autosomal dmrt1a gene is also able to regulate transcription of its duplicated paralog by binding to a unique target Dmrt1 site nested within the dmrt1bY proximal promoter region. We could trace back this novel regulatory element to a highly conserved sequence within a new type of TE that inserted into the upstream region of dmrt1bY shortly after the duplication event. Our data provide functional evidence for a role of TEs in transcriptional network rewiring for sub- and/or neo-functionalization of duplicated genes. In the particular case of dmrt1bY, this contributed to create new hierarchies of sex-determining genes.}, subject = {Gen}, language = {en} } @article{MergetWolf2010, author = {Merget, Benjamin and Wolf, Matthias}, title = {A molecular phylogeny of Hypnales (Bryophyta) inferred from ITS2 sequence-structure data}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67997}, year = {2010}, abstract = {Background: Hypnales comprise over 50\% of all pleurocarpous mosses. They provide a young radiation complicating phylogenetic analyses. To resolve the hypnalean phylogeny, it is necessary to use a phylogenetic marker providing highly variable features to resolve species on the one hand and conserved features enabling a backbone analysis on the other. Therefore we used highly variable internal transcribed spacer 2 (ITS2) sequences and conserved secondary structures, as deposited with the ITS2 Database, simultaneously. Findings: We built an accurate and in parts robustly resolved large scale phylogeny for 1,634 currently available hypnalean ITS2 sequence-structure pairs. Conclusions: Profile Neighbor-Joining revealed a possible hypnalean backbone, indicating that most of the hypnalean taxa classified as different moss families are polyphyletic assemblages awaiting taxonomic changes.}, subject = {Moose}, language = {en} } @article{NeskePrifertScheineretal.2010, author = {Neske, Florian and Prifert, Christiane and Scheiner, Barbara and Ewald, Moritz and Schubert, Joerg and Opitz, Andreas and Weissbrich, Benedikt}, title = {High prevalence of antibodies against polyomavirus WU, polyomavirus KI, and human bocavirus in German blood donors}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67941}, year = {2010}, abstract = {Background: DNA of the polyomaviruses WU (WUPyV) and KI (KIPyV) and of human bocavirus (HBoV) has been detected with varying frequency in respiratory tract samples of children. However, only little is known about the humoral immune response against these viruses. Our aim was to establish virus-specific serological assays and to determine the prevalence of immunoglobulin G (IgG) against these three viruses in the general population. Methods: The capsid proteins VP1 of WUPyV and KIPyV and VP2 of HBoV were cloned into baculovirus vectors and expressed in Sf9 insect cells. IgG antibodies against WUPyV VP1, KIPyV VP1, and HBoV VP2 were determined by immunofluorescence assays in 100 plasma samples of blood donors. Results: The median age of the blood donors was 31 years (range 20 - 66 yrs), 52\% were male. 89\% of the samples were positive for WUPyV IgG (median age 31 yrs, 49.4\% male), 67\% were positive for KIPyV IgG (median age 32 yrs, 46.3\% male), and 76\% were positive for HBoV IgG (median age 32 yrs, 51.3\% male). For WUPyV and HBoV, there were no significant differences of the seropositivity rates with respect to age groups or gender. For KIPyV, the seropositivity rate increased significantly from 59\% in the age group 20 - 29 years to 100\% in the agegroup > 50 years. Conclusions: High prevalences of antibodies against WUPyV, KIPyV, and HBoV were found in plasma samples of healthy adults. The results indicate that primary infection with these viruses occurs during childhood or youth. For KIPyV, the seropositivity appears to increase further during adulthood.}, subject = {Polyoma-Virus}, language = {en} } @article{NeumannHaefelinRethwilmBaueretal.1983, author = {Neumann-Haefelin, D. and Rethwilm, Axel and Bauer, G. and Gudat, F. and zur Hausen, H.}, title = {Characterization of a foamy virus isolated from Cercopithecus aethiops lymphoblastoid cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61538}, year = {1983}, abstract = {A virus derived from cells of a Iymphoblastoid line originating from the lymph node of a healthy African green monkey was characterized as a typical member of the foamy virus subgroup of rctroviridac by its morphological, physicochemical, biological and biochemical properties (reverse transcriptase actvity). Besides the usual host range of foamy viruses, the isolated strain revealed a remarkable T -lymphotropism, distinguishing it from the prototypes of foamy viruses previously isolated from African green monkeys. Two foamy virus infectious are demonstrated in human contacts of the African green monkey colony, with the animal barbauring the isolate.}, subject = {Virologie}, language = {en} } @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{RethwilmDaraiRoesenetal.1987, author = {Rethwilm, Axel and Darai, G. and R{\"o}sen, A. and Maurer, Bernd and Fl{\"u}gel, Rolf M.}, title = {Molecular cloning of the genome of human spumaretrovirus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61518}, year = {1987}, abstract = {DNA ofhuman spumaretrovirus (HSRV) was cloned from both cDNA and from viral DNA into phage A and bacterial plasmid vectors. The recombinant plasm.ids harboring viral DNA were characterized by Southern blot hybridization and restriction mapping. Physical maps were constructed from cDNA and found to be colinear with the restriction maps obtained from viral DNA. The recombinant clones isolated contained viral DNA inserts which rangein size from 2.2 kb to 15.4 kb. The recombinant clones allowed to construct a physical map of the complete HSRV provirus of 12.2 kb.}, 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} } @article{RethwilmBaunachNetzeretal.1990, author = {Rethwilm, Axel and Baunach, Gerald and Netzer, Kai O. and Maurer, Bernd and Borisch, Bettina and ter Meulen, V.olker}, title = {Infectious DNA of the human spumaretrovirus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61495}, year = {1990}, abstract = {An infectious molecular clone (pHSRV) of the human Spumaretrovirus (HSRV) was constructed using viral DNA and cDNA clones. The infectivity of pHSRV was proven by transfection of cell cultures and subsequent infection of susceptible cultures with cell free transfection derlved virus. pHSRV derived virus produced foamy virus typical cytopathic effects in susceptible cultures. lnfected cells could be stained specifically with foamy virus antisera by means of indirect immunofluorescence. Radiolmmunoprecipltatlon revealed the presence of characteristic HSRV structural proteins in pHSRV infected cultures. By cotransfection of pHSRV and an indicator plasmid it was found that pHSRV is able to transactivate the viral L TR. Viral transcripts were found to be approximately 200 bases Ionger in pHSRV infected cultures compared to wildtype infected cultures. This difference is most likely due to an Insertion of DNA of non-viral origin ln the U3 region of the 3'L TR of the infectious clone.}, 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{NetzerRethwilmMaureretal.1990, author = {Netzer, Kai O. and Rethwilm, Axel and Maurer, Bernd and ter Meulen, Volker}, title = {Identification of the major immunogenic structural proteins of human foamy virus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61477}, year = {1990}, abstract = {We have identified the major immunogenic structural proteins of the human foamy virus (HFV), a distinct member of the foamy virus subfamily of Retroviridae. Radiolabelied viral proteins were immunoprecipitated from HFV -infected cells by foamy virus antisera of human and non-human primate origin. Precipitated viral proteins were in the range of 31 K to 170K. Labelling of proteins with [\(^{14}\)C]glucosamine or with [\(^{35}\)S]methionine in the presence oftunicamycin, as well as endo-ß-N-acetylglycosaminidase Hand F treatment of [\(^{35}\)S]methionine-labelled proteins, revealed three viral glycoproteins of approximately 170K, 130K and 47K, most likely representing the env gene-encoded precursor, the surface glycoprotein and the transmembrane protein of HFV, respectively.}, 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} }