@article{BodemRethwilm2013,
  author    = {Bodem, Jochen and Rethwilm, Axel},
  title     = {Evolution of Foamy Viruses: The Most Ancient of All Retroviruses},
  series = {Viruses},
  journal   = {Viruses},
  doi       = {10.3390/v5102349},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97312},
  year      = {2013},
  abstract  = {Recent evidence indicates that foamy viruses (FVs) are the oldest retroviruses (RVs) that we know and coevolved with their hosts for several hundred million years. This coevolution may have contributed to the non-pathogenicity of FVs, an important factor in development of foamy viral vectors in gene therapy. However, various questions on the molecular evolution of FVs remain still unanswered. The analysis of the spectrum of animal species infected by exogenous FVs or harboring endogenous FV elements in their genome is pivotal. Furthermore, animal studies might reveal important issues, such as the identification of the FV in vivo target cells, which than require a detailed characterization, to resolve the molecular basis of the accuracy with which FVs copy their genome. The issues of the extent of FV viremia and of the nature of the virion genome (RNA vs. DNA) also need to be experimentally addressed.},
  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{GundaKasangKidenyaetal.2013,
  author    = {Gunda, Daniel W. and Kasang, Christa and Kidenya, Benson R. and Kabangila, Rodrick and Mshana, Stephen E. and Kidola, Jeremiah and Kalluvya, Samuel E. and Kongola, Gilbert W. and Klinker, Hartwig},
  title     = {Plasma Concentrations of Efavirenz and Nevirapine among HIV-Infected Patients with Immunological Failure Attending a Tertiary Hospital in North-Western Tanzania},
  series = {PLOS ONE},
  volume    = {8},
  journal   = {PLOS ONE},
  number    = {9},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0075118},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128456},
  pages     = {e75118},
  year      = {2013},
  abstract  = {Background: Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. Materials and Methods: A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. Results: Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3\%), 76/152 (50.0\%) and 33/152 (21.7\%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supratherapeutic ARV plasma drug concentrations. Conclusion: There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine therapeutic drug monitoring (TDM) could assist identifying these patients early and making timely correction to avoid virological failure, poor immunological outcome and prevent associated drug toxicities. Nonetheless, ARV adherence should be strictly emphasized on HIV patients with immunological failure.},
  language  = {en}
}
@article{HornSchellerduPlessisetal.2013,
  author    = {Horn, Anne and Scheller, Carsten and du Plessis, Stefan and Arendt, Gabriele and Nolting, Thorsten and Joska, John and Sopper, Sieghart and Maschke, Matthias and Obermann, Mark and Husstedt, Ingo W. and Hain, Johannes and Maponga, Tongai and Riederer, Peter and Koutsilieri, Eleni},
  title     = {Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals},
  series = {Journal of Neural Transmission},
  volume    = {120},
  journal   = {Journal of Neural Transmission},
  doi       = {10.1007/s00702-013-1086-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132385},
  pages     = {1411-1419},
  year      = {2013},
  abstract  = {Dysfunction of dopaminergic neurotransmission has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-na{\"i}ve HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, suggesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interestingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95 \% CI 1.72-8.96; p = 0.001, Fishers exact test). 42.6 \% HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5 \% uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9 \%, respectively, in Germany (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease.},
  language  = {en}
}
@article{KoutsilieriLutzScheller2013,
  author    = {Koutsilieri, E. and Lutz, M. B. and Scheller, C.},
  title     = {Autoimmunity, dendritic cells and relevance for Parkinson's disease},
  series = {Journal of Neural Transmission},
  volume    = {120},
  journal   = {Journal of Neural Transmission},
  doi       = {10.1007/s00702-012-0842-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132308},
  pages     = {75-81},
  year      = {2013},
  abstract  = {Innate and adaptive immune responses in neurodegenerative diseases have become recently a focus of research and discussions. Parkinson's disease (PD) is a neurodegenerative disorder without known etiopathogenesis. The past decade has generated evidence for an involvement of the immune system in PD pathogenesis. Both inflammatory and autoimmune mechanisms have been recognized and studies have emphasized the role of activated microglia and T-cell infiltration. In this short review, we focus on dendritic cells, on their role in initiation of autoimmune responses, we discuss aspects of neuroinflammation and autoimmunity in PD, and we report new evidence for the involvement of neuromelanin in these processes.},
  language  = {en}
}
@article{KuehlhornRathSchmoeckeletal.2013,
  author    = {K{\"u}hlhorn, Franziska and Rath, Matthias and Schmoeckel, Katrin and Cziupka, Katharina and Nguyen, Huu Hung and Hildebrandt, Petra and H{\"u}nig, Thomas and Sparwasser, Tim and Huehn, Jochen and P{\"o}tschke, Christian and Br{\"o}ker, Barbara M.},
  title     = {\(Foxp3^+\) Regulatory T Cells Are Required for Recovery from Severe Sepsis},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0065109},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130940},
  pages     = {e65109},
  year      = {2013},
  abstract  = {The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of \(CD4^+Foxp3^+\) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.},
  language  = {en}
}
@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{PrifertStrengKrempletal.2013,
  author    = {Prifert, Christiane and Streng, Andrea and Krempl, Christine D. and Liese, Johannes and Weissbrich, Benedikt},
  title     = {Novel Respiratory Syncytial Virus A Genotype, Germany, 2011-2012},
  series = {Emerging Infectious Diseases},
  volume    = {19},
  journal   = {Emerging Infectious Diseases},
  number    = {6},
  doi       = {10.3201/eid1906.121582},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129041},
  pages     = {1029-1030},
  year      = {2013},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{RiedelMofoloAvotaetal.2013,
  author    = {Riedel, Alice and Mofolo, Boitumelo and Avota, Elita and Schneider-Schaulies, Sibylle and Meintjes, Ayton and Mulder, Nicola and Kneitz, Susanne},
  title     = {Accumulation of Splice Variants and Transcripts in Response to PI3K Inhibition in T Cells},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {2},
  doi       = {10.1371/journal.pone.0050695},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130335},
  pages     = {e50695},
  year      = {2013},
  abstract  = {Background Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. Methods To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. Results Applying our algorithm to the data, 9\% of the genes were assigned as AS, while only 3\% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. Conclusions PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression.},
  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}
}