@article{SporbertCseresnyesHeidbrederetal.2013,
  author    = {Sporbert, Anje and Cseresnyes, Zoltan and Heidbreder, Meike and Domaing, Petra and Hauser, Stefan and Kaltschmidt, Barbara and Kaltschmidt, Christian and Heilemann, Mike and Widera, Darius},
  title     = {Simple Method for Sub-Diffraction Resolution Imaging of Cellular Structures on Standard Confocal Microscopes by Three-Photon Absorption of Quantum Dots},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0064023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130963},
  pages     = {e64023},
  year      = {2013},
  abstract  = {This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres) and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts.},
  language  = {en}
}
@article{SpinnerWilleSchwerdtfegeretal.2015,
  author    = {Spinner, Christoph D and Wille, Florian and Schwerdtfeger, Christiane and Thies, Philipp and Tanase, Ursula and Von Figura, Guido and Schmid, Roland M and Heinz, Werner J and Klinker, Hartwig Hf},
  title     = {Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and MAI infection: some new conflicting data},
  series = {AIDS Research and Therapy},
  volume    = {12},
  journal   = {AIDS Research and Therapy},
  number    = {1},
  doi       = {10.1186/s12981-014-0041-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144058},
  year      = {2015},
  abstract  = {Background: While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5'-diphosph-gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power. Methods: We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used. Results: High intra-personal variability in raltegravir serum levels was seen. Comparable C\(_{max}\) concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While C\(_{max}\) seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC(12) is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels. Conclusions: We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations.},
  language  = {en}
}
@phdthesis{Sippel2010,
  author    = {Sippel, Martin},
  title     = {Computational Structure-based Design Approaches: Targeting HIV-1 Integrase and the Macrophage Infectivity Potentiator of Legionella pneumophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51247},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Die vorliegende Arbeit thematisiert das computergest{\"u}tzte strukturbasierte Design auf dem Gebiet der HIV-1-Integrase und des Macrophage Infectivity Potentiator (MIP) von Legionella pneumophila. Die durchgef{\"u}hrten Studien geben wertvolle Aufschl{\"u}sse {\"u}ber den Wirk-mechanismus einer bekannten Integrase-Inhibitorenklasse and zeigt dar{\"u}ber hinaus einen neuartigen Ansatz zur Integrase-Inhibition auf. Im Falle des MIP-Enzyms konnten zwei niedermolekulare Inhibitoren ermittelt werden. Die Integrase-Studien ergaben wertvolle Informationen im Hinblick auf das Design neuer Inhibitoren. Docking-Experimente konnten die Hypothese weiter untermauern, nach der die Klasse der Diketos{\"a}ure-Inhibitoren nicht als freie Liganden, sondern als Metallion-Komplexe an das aktive Zentrum der Integrase binden. Die Ergebnisse dieser Studie helfen dabei, das Verst{\"a}ndnis {\"u}ber den Wirkmechanismus dieser wichtigen Klasse von Integrase-Inhibitoren weiter zu vertiefen. Um der Entwicklung von Integrase-Inhibitoren einen neuen Impuls zu geben, wurde eine neue Strategie zur Inhibition dargelegt: Anstatt an das aktive Zentrum soll eine neue Inhibitor-Klasse an das Dimerisierungs-Interface eines Integrase-Monomers binden, die katalytisch notwendige Dimerisierung verhindern und somit die enzymatische Aktivit{\"a}t st{\"o}ren. Das Hauptproblem hierbei bestand in den fehlenden Strukturdaten des freien Monomers. Hierzu wurden Molekulardynamik-Simulationen durchgef{\"u}hrt, um n{\"a}here strukturelle Informationen zu erhalten. Momentaufnahmen unterschiedlicher Konformationen dienten als Input-Strukturen f{\"u}r eine Docking-Studie mit dem peptidischen Inhibitor YFLLKL, um dessen Bindemodus aufzukl{\"a}ren. Hierbei zeigte sich, dass dieser Ligand an eine Interface-Konformation bindet, die durch eine Y-f{\"o}rmige Bindestelle charakterisiert ist. Im n{\"a}chsten Schritt sollte diese Protein-Konformation mit kleinen, nicht-peptidischen Molek{\"u}len adressiert werden. Die erste Strategie bestand darin, ein Pharmakophor-Modell zu erstellen, das zur Suche nach Molek{\"u}len mit einer guten Komplementarit{\"a}t zur Y-f{\"o}rmigen Bindetasche geeignet ist. Das folgende virtuelle Screening ergab zehn Verbindungen, die eine gute Komplementarit{\"a}t und g{\"u}nstige hydrophobe Wechselwirkungen aufwiesen. Leider zeigte keine der Verbindungen eine reproduzierbare Aktivit{\"a}t im Integrase-Assay. Hierbei verbleiben jedoch gewisse Zweifel, da in dem Assay die Zugabe von BSA vorgeschrieben war, das m{\"o}glicherweise die hydrophoben Inhibitor-Kandidaten gebunden hat. Die erw{\"a}hnte erste Strategie wurde {\"u}berdacht: In einem zweiten Ansatz galt die Hauptaufmerksamkeit der Abs{\"a}ttigung von wasserstoffbr{\"u}ckenbildenden Resten. Diese waren zuvor von den eher hydrophoben Verbindungen nicht optimal abges{\"a}ttigt worden. Zwei Pharmakophor-Modelle wurden erstellt und in einem virtuellen Screening eingesetzt: Docking-Studien der Hits zeigten jedoch, dass nach wie vor viele wasserstoffbr{\"u}ckenbildende Reste des Proteins nicht vom Liganden abges{\"a}ttigt wurden. Nach abschließender eingehender Betrachtung der Bindemoden der verbliebenen Molek{\"u}le aus dem virtuellen Screening konnten nur acht f{\"u}r weitere Testungen ausgew{\"a}hlt werden (Ergebnisse der experimentellen Testung durch Kooperationspartner stehen noch aus). Diese geringe „Ausbeute" an geeigneten Verbindungen f{\"u}r das Integrase-Dimerisierungsinterface zeigt, wie schwer dieses Target zu adressieren ist: Das Interface weist eine schnell wechselnde Abfolge von basischen, sauren und hydrophoben Resten auf. Im Gegensatz zu anderen Protein-Protein-Interfaces zeigt das Integrase-Interface keine „aufger{\"a}umte" Bindetasche mit klar voneinander getrennten hydrophoben und hydrophilen Bereichen. F{\"u}r das zweite Enzym, MIP, konnten mit Hilfe des strukturbasierten Designs zwei niedermolekulare Inhibitoren gefunden werden. Beide Verbindungen f{\"u}hrten zu einer deutlichen Abnahme der katalytischen Aktivit{\"a}t. Soweit bekannt, sind bisher keinerlei niedermolekulare MIP-Inhibitoren ver{\"o}ffentlicht. Der Vergleich von MIP mit der humanen PPIase FKBP12 zeigte eine gr{\"o}ßtenteils {\"a}hnliche Tasche, die jedoch einen entscheidenden Unterschied aufweist, n{\"a}mlich in der Orientierung des Restes Tyr109. Die detaillierte Betrachtung der Strukturdaten beider Enzyme konnte schließlich eine Erkl{\"a}rung liefern, warum ein ketoacyl-substituiertes Pipecolinderivat nicht an MIP bindet, ein sulfonsubstituiertes Pipecolinderivat hingegen das Enzym inhibiert. Die Erkenntnisse {\"u}ber das Inhibitoren-Design f{\"u}r Legionella-MIP k{\"o}nnen auch auf andere Organismen (z.B. Trypanosomen) {\"u}bertragen werden, bei denen ebenfalls (homologes) MIP ein Pathogenit{\"a}tsfaktor ist.},
  subject      = {Legionella pneumophila},
  language  = {en}
}
@article{ShityakovFoersterRethwilmetal.2014,
  author    = {Shityakov, Sergey and F{\"o}rster, Carola and Rethwilm, Axel and Dandekar, Thomas},
  title     = {Evaluation and Prediction of the HIV-1 Central Polypurine Tract Influence on Foamy Viral Vectors to Transduce Dividing and Growth-Arrested Cells},
  doi       = {10.1155/2014/487969},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112763},
  year      = {2014},
  abstract  = {Retroviral vectors are potent tools for gene delivery and various biomedical applications. To accomplish a gene transfer task successfully, retroviral vectors must effectively transduce diverse cell cultures at different phases of a cell cycle. However, very promising retroviral vectors based on the foamy viral (FV) backbone lack the capacity to efficiently transduce quiescent cells. It is hypothesized that this phenomenon might be explained as the inability of foamy viruses to form a pre-integration complex (PIC) with nuclear import activity in growth-arrested cells, which is the characteristic for lentiviruses (HIV-1). In this process, the HIV-1 central polypurine tract (cPPT) serves as a primer for plus-strand synthesis to produce a "flap" element and is believed to be crucial for the subsequent double-stranded cDNA formation of all retroviral RNA genomes. In this study, the effects of the lentiviral cPPT element on the FV transduction potential in dividing and growth-arrested (G1/S phase) adenocarcinomic human alveolar basal epithelial (A549) cells are investigated by experimental and theoretical methods. The results indicated that the HIV-1 cPPT element in a foamy viral vector background will lead to a significant reduction of the FV transduction and viral titre in growth-arrested cells due to the absence of PICs with nuclear import activity.},
  subject      = {Evaluation},
  language  = {en}
}
@article{SeifEinseleLoeffler2019,
  author    = {Seif, Michelle and Einsele, Hermann and L{\"o}ffler, J{\"u}rgen},
  title     = {CAR T cells beyond cancer: hope for immunomodulatory therapy of infectious diseases},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  number    = {2711},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2019.02711},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195596},
  year      = {2019},
  abstract  = {Infectious diseases are still a significant cause of morbidity and mortality worldwide. Despite the progress in drug development, the occurrence of microbial resistance is still a significant concern. Alternative therapeutic strategies are required for non-responding or relapsing patients. Chimeric antigen receptor (CAR) T cells has revolutionized cancer immunotherapy, providing a potential therapeutic option for patients who are unresponsive to standard treatments. Recently two CAR T cell therapies, Yescarta® (Kite Pharma/Gilead) and Kymriah® (Novartis) were approved by the FDA for the treatments of certain types of non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia, respectively. The success of adoptive CAR T cell therapy for cancer has inspired researchers to develop CARs for the treatment of infectious diseases. Here, we review the main achievements in CAR T cell therapy targeting viral infections, including Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus, Human Cytomegalovirus, and opportunistic fungal infections such as invasive aspergillosis.},
  language  = {en}
}
@inproceedings{SchwinnRethwilmEsersetal.1990,
  author    = {Schwinn, Andreas and Rethwilm, Axel and Esers, Stefan and Borisch, Bettina and ter Meulen, Volker},
  title     = {Interaction of HIV-1 and HHV-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86415},
  year      = {1990},
  abstract  = {No abstract available.},
  subject      = {HIV},
  language  = {en}
}
@article{SchneiderSchauliesSchumacherWiggeretal.2021,
  author    = {Schneider-Schaulies, Sibylle and Schumacher, Fabian and Wigger, Dominik and Sch{\"o}l, Marie and Waghmare, Trushnal and Schlegel, Jan and Seibel, J{\"u}rgen and Kleuser, Burkhard},
  title     = {Sphingolipids: effectors and Achilles heals in viral infections?},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {9},
  issn      = {2073-4409},
  doi       = {10.3390/cells10092175},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245151},
  year      = {2021},
  abstract  = {As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.},
  language  = {en}
}
@article{RudovickBraunerEnglertetal.2018,
  author    = {Rudovick, Ladius and Brauner, Jan M. and Englert, Johanna and Seemann, Carolina and Plugaru, Karina and Kidenya, Benson R. and Kalluvya, Samuel E. and Scheller, Carsten and Kasang, Christa},
  title     = {Prevalence of pretreatment HIV drug resistance in Mwanza, Tanzania},
  series = {Journal of Antimicrobial Chemotherapy},
  volume    = {73},
  journal   = {Journal of Antimicrobial Chemotherapy},
  number    = {12},
  doi       = {10.1093/jac/dky332},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227124},
  pages     = {3476-3481},
  year      = {2018},
  abstract  = {Background: In a 2008-10 study, we found a pretreatment HIV drug resistance (PDR) prevalence of 18.2\% in patients at Bugando Medical Centre (BMC) in Mwanza, Tanzania. Objectives: To determine the prevalence of PDR and transmitted HIV drug resistance (TDR) in patients visiting the BMC from 2013 to 2015. Methods: Adult outpatients were sequentially enrolled into two groups, separated by whether they were initiating ART. Previous exposure to antiretroviral drugs, except for prevention of mother-to-child transmission, was an exclusion criterion. HIV pol sequences were analysed according to WHO guidelines for surveillance of PDR and TDR. Results: Two hundred and thirty-five sequences were analysed (138 ART initiators, 97 non-initiators). The prevalence of PDR was 4.7\% (95\% CI 2.6\%-8.2\%) overall, 3.1\% (95\% CI 1.1\%-8.7\%) for non-initiators and 5.8\% (95\% CI 3.0\%-11.0\%) for ART initiators. PDR to NNRTIs and nucleoside or nucelotide reverse transcriptase inhibitors was found in 3.0\% (95\% CI 1.5\%-6.0\%) and 1.7\% (95\% CI 0.7\%-4.3\%) of patients, respectively. Resistance to PIs was not observed. The prevalence of TDR was 6.0\% (95\% CI 3.6\%-9.8\%). Conclusions: Prevalence of PDR significantly decreased compared with 2008-10 and was below the WHO-defined threshold for triggering a public health response. National and systematic surveillance is needed to inform Tanzania's public health strategy.},
  language  = {en}
}
@inproceedings{RethwilmBaunachMorietal.1990,
  author    = {Rethwilm, Axel and Baunach, Gerald and Mori, Kazuyasu and ter Meulen, Volker},
  title     = {Transactivation of HIV by human spumaretrovirus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86436},
  year      = {1990},
  abstract  = {To study the activation of HIV by human spumaretrovirus (HSRV) the long terminal repeats (LTRs) of HSRV, HIVl and HIV2 were examined with respect to their ability to function as transcriptional promoters in virus infected and uninfected cells. Transient transfections using plasmids in which the L TRs of the three viruses were coupled to the bacterial chloramphenicol acetyltransferase (CA T) gene revealed (i) the level of cat gene expression directed by the HSRV LTR was markedly increased in HSRV infected cells compared to uninfected cells, (ii) cat gene expression driven by the HIV1 LTR, but not by the HIV2 LTR could be enhanced upon HSRV infection, whereas (iii) neither in HIV1 nor in HIV2 infected cells an effect on HSRV LTR driven cat geneexpression was detected.},
  subject      = {HIV},
  language  = {en}
}
@article{ProttengeierKoutsilieriScheller2014,
  author    = {Prottengeier, Johannes and Koutsilieri, Eleni and Scheller, Carsten},
  title     = {The effects of opioids on HIV reactivation in latently-infected T-lymphoblasts},
  series = {AIDS Research and Therapy},
  volume    = {11},
  journal   = {AIDS Research and Therapy},
  number    = {17},
  issn      = {1742-6405},
  doi       = {10.1186/1742-6405-11-17},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115860},
  year      = {2014},
  abstract  = {Background: Opioids may have effects on susceptibility to HIV-infection, viral replication and disease progression. Injecting drug users (IDU), as well as anyone receiving opioids for anesthesia and analgesia may suffer the clinical consequences of such interactions. There is conflicting data between in vitro experiments showing an enhancing effect of opioids on HIV replication and clinical data, mostly showing no such effect. For clarification we studied the effects of the opioids heroin and morphine on HIV replication in cultured CD4-positive T cells at several concentrations and we related the observed effects with the relevant reached plasma concentrations found in IDUs. Methods: Latently-infected ACH-2 T lymphoblasts were incubated with different concentrations of morphine and heroine. Reactivation of HIV was assessed by intracellular staining of viral Gag p24 protein and subsequent flow cytometric quantification of p24-positive cells. The influence of the opioid antagonist naloxone and the antioxidants N-acetyl-cysteine (NAC) and glutathione (GSH) on HIV reactivation was determined. Cell viability was investigated by 7-AAD staining and flow cytometric quantification. Results: Morphine and heroine triggered reactivation of HIV replication in ACH-2 cells in a dose-dependent manner at concentrations above 1 mM (EC50 morphine 2.82 mM; EC50 morphine 1.96 mM). Naloxone did not interfere with heroine-mediated HIV reactivation, even at high concentrations (1 mM). Opioids also triggered necrotic cell death at similar concentrations at which HIV reactivation was observed. Both opioid-mediated reactivation of HIV and opioid-triggered cell death could be inhibited by the antioxidants GSH and NAC. Conclusions: Opioids reactivate HIV in vitro but at concentrations that are far above the plasma levels of analgesic regimes or drug concentrations found in IDUs. HIV reactivation was mediated by effects unrelated to opioid-receptor activation and was tightly linked to the cytotoxic activity of the substances at millimolar concentrations, suggesting that opioid-mediated reactivation of HIV was due to accompanying effects of cellular necrosis such as activation of reactive oxygen species and NF-kB.},
  language  = {en}
}