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Lee H.W.,Korea University | Vaheri A.,University of Helsinki | Schmaljohn C.S.,Molecular Virology
Virus Research | Year: 2014

We three authors, the two past presidents (HWL and AV) and the current president (CSS) of the International Society for Hantaviruses (ISH) have attended most of the nine International Conferences on HFRS, HPS and Hantaviruses (Table 1). These conferences have provided a forum for a synergistic group of clinicians, basic researchers, mammalogists, epidemiologists and ecologists to share their expertise and interests in all aspects of hantavirus research. Much of what is now hantavirus dogma was only conjecture when HWL organized the first conference in Seoul, Korea in 1989. Herein, we provide our reflections on key events in hantavirus research. As we come from distinct areas of the world and have had individual historical experiences, we certainly have our own geocentric opinions about the key events. Nevertheless, we agree that the discovery of hantaviruses has taken an interesting and unpredictable track to where we are today. © 2014 .

Heisel S.,Saarland University | Habel N.C.,Saarland University | Schuetz N.,Saarland University | Ruggieri A.,Molecular Virology | Meese E.,Saarland University
BMC Molecular Biology | Year: 2010

Background: In eukaryotes the transcription initiation by RNA polymerase II requires numerous general and regulatory factors including general transcription factors. The general transcription factor TFIIF controls the activity of the RNA polymerase II both at the initiation and elongation stages. The glioma amplified sequence 41 (GAS41) has been associated with TFIIF via its YEATS domain.Results: Using GST pull-down assays, we demonstrated that GAS41 binds to both, the small subunit (RAP30) and the large subunit (RAP74) of TFIIF in vitro. The in vivo interaction of GAS41 and endogenous RAP30 and RAP74 was confirmed by co-immunoprecipitation. GAS41 binds to two non-overlapping regions of the C-terminus of RAP30. There is also an ionic component to the binding between GAS41 and RAP30. There was no evidence for a direct interaction between GAS41 and TBP or between GAS41 and RNA polymerase II.Conclusions: Our results demonstrate binding between endogenous GAS41 and the endogenous TFIIF subunits (RAP30 and RAP74). Since we did not find evidence for a binding of GAS41 to TBP or RNA polymerase II, GAS41 seems to preferentially bind to TFIIF. GAS41 that does not contain a DNA-binding domain appears to be a co-factor of TFIIF. © 2010 Heisel et al; licensee BioMed Central Ltd.

Four capules of Tamiflu are pictured on a Tamiflu box in Burbank, California, January 31, 2013. REUTERS/Fred Prouser More LONDON, Oct 8 (Reuters) - - Scientists still don't know if two commonly-used flu drugs -- Roche's Tamiflu and GlaxoSmithKline's Relenza -- really work in seasonal or pandemic flu outbreaks and say robust clinical trials are urgently needed to find out. While such medicines are stockpiled by governments around the world and were widely used in the 2009/2010 H1N1 "swine flu" pandemic, no randomised trials were conducted then, so evidence is scant on how effective that approach was. Publishing a report on the use of such antiviral drugs - known as neuraminidase inhibitors - against flu, experts co-led by Wellcome Trust director Jeremy Farrar said this had been a huge wasted opportunity and one that should not happen again. "In the H1N1 pandemic, a lot of Tamiflu was taken and distributed, but we have no idea whether that was right," said Chris Bulter, an expert on clinical trials at Britain's Oxford University who co-led the review. "Until we do the trials we don't really know what we should be doing - and we've wasted huge opportunities in the past by not randomising patients early on in pandemics." In their report on the evidence for using antivirals in seaonal flu, the experts found the medicines do significantly reduce deaths in hospitalised patients, particularly in those who start treatment within 48 hours of first becoming ill. This could be critical in a flu epidemic, Farrar and Butler told reporters at a briefing in London. Evidence also suggests anitivirals can reduce symptoms in seasonal flu by between 14 and 17 hours, they said, but it does not support routine use of the drugs for all patients since, unless the case is particularly serious, the benefits may not outweigh the side-effect risks. The report was produced in response to a government request for an evidence-based report to inform future policy decisions. Jonathan Ball, a professor of Molecular Virology at the University of Nottingham who was not involved in the report, said it raised some crucial issues: "We know the virus can become resistant to these antivirals so it is really important they are only used where there is clear evidence of their value," he said. "Also these drugs aren’t cheap, so government(s) could end up generating profit for drugs companies when there is no clear evidence that it is money well spent." "The evidence-base isn't as strong as it should be. We risk misusing these drugs until this...knowledge gap is filled."

Pawella L.M.,University of Heidelberg | Hashani M.,University of Heidelberg | Eiteneuer E.,University of Heidelberg | Renner M.,University of Heidelberg | And 3 more authors.
Journal of Hepatology | Year: 2014

Background & Aims Hepatocellular steatosis is the most frequent liver disease in the western world and may develop further to steatohepatitis, liver cirrhosis and hepatocellular carcinoma. We have previously shown that lipid droplet (LD)-associated proteins of the perilipin/PAT-family are differentially expressed in hepatocyte steatosis and that perilipin is expressed de novo. The aim of this study was to determine the conditions for the temporal regulation of de novo synthesis of perilipin in vitro and in vivo. Methods Immunohistochemical PAT-analysis was performed with over 120 liver biopsies of different etiology and duration of steatosis. Steatosis was induced in cultured hepatocytic cells with combinations of lipids, steatogenic substances and DMSO for up to 40 days under conditions of stable down-regulation of adipophilin and/or TIP47. Results Whereas perilipin and adipophilin were expressed in human chronic liver disease irrespective of the underlying etiology, in acute/microvesicular steatosis TIP47, and MLDP were recruited from the cytoplasm to LDs, adipophilin was strongly increased, but perilipin was virtually absent. In long-term steatosis models in vitro, TIP47, MLDP, adipophilin, and finally perilipin were gradually induced. Perilipin and associated formation of LDs were intricately regulated on the transcriptional (PPARs, C/EBPs, SREBP), post-transcriptional, and post-translational level (TAG-amount, LD-fusion, phosphorylation-dependent lipolysis). In long-term steatosis models under stable down-regulation of adipophilin and/or TIP47, MLDP substituted for TIP47, and perilipin for adipophilin. Conclusions LD-maturation in hepatocytes in vivo and in vitro involves sequential expression of TIP47, MLDP, adipophilin and finally perilipin. Thus, perilipin might be used for the differential diagnosis of chronic vs. acute steatosis. © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Fiorina L.,Molecular Virology | Ricotti M.,Oncology Section | Vanoli A.,University of Pavia | Luinetti O.,University of Pavia | And 8 more authors.
Infectious Agents and Cancer | Year: 2014

Background: Environmental factors may play a role in colon cancer. In this view, several studies investigated tumor samples for the presence of various viral DNA with conflicting results. Findings. We undertook a systematic DNA analysis of 44 consecutive, prospectively collected primary tumor samples by real time and qualitative PCR for viruses of known or potential oncogenic role in humans, including polyomavirus (JCV, BKV, Merkel cell polyomavirus), HPV, HTLV, HHV-8 and EBV. Negative controls consisted of surgical resection margins. No evidence of genomic DNA fragments from tested virus were detected, except for EBV, which was found in a significant portion of tumors (23/44, 52%). Real-time PCR showed that EBV DNA was present at a highly variable content (median 258 copies in 105 cells, range 15-4837). Presence of EBV DNA had a trend to be associated with high lymphocyte infiltration (p = 0.06, χ2 test), and in situ hybridization with EBER1-2 probes revealed latency in a fraction of these lymphoid cells, with just a few scattered plasma cells positive for BZLF-1, an immediate early protein expressed during lytic replication. LMP-1 expression was undetectable by immunohistochemistry. Conclusions: These results argue against a significant involvement of the tested oncogenic viruses in established colon cancer. © 2014 Fiorina et al.; licensee BioMed Central Ltd.

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