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  • BEEHIVE Collaboration; Wymant, Chris; Blanquart, Francois; Golubchik, Tanya; Gall, Astrid; Bakker, Margreet; Bezemer, Daniela; Croucher, Nicholas J.; Hall, Matthew; Hillebregt, Mariska; Ong, Swee Hoe; Ratmann, Oliver; Albert, Jan; Bannert, Norbert; Fellay, Jacques; Fransen, Katrien; Gourlay, Annabelle; Grabowski, M. Kate; Gunsenheimer-Bartmeyer, Barbara; Gunthard, Huldrych F.; Kivelä, Pia; Kouyos, Roger; Laeyendecker, Oliver; Liitsola, Kirsi; Meyer, Laurence; Porter, Kholoud; Ristola, Matti; van Sighem, Ard; Berkhout, Ben; Cornelissen, Marion; Kellam, Paul; Reiss, Peter; Fraser, Christophe (2018)
    Studying the evolution of viruses and their molecular epidemiology relies on accurate viral sequence data, so that small differences between similar viruses can be meaningfully interpreted. Despite its higher throughput and more detailed minority variant data, next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of large between-and within-host diversity, including frequent indels, may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to pre-process reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with the user's choice of existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We used shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read whole-genome data produced with the Illumina platform, for sixty-five existing publicly available samples and fifty new samples. We show the systematic superiority of mapping to shiver's constructed reference compared with mapping the same reads to the closest of 3,249 real references: median values of 13 bases called differently and more accurately, 0 bases called differently and less accurately, and 205 bases of missing sequence recovered. We also successfully applied shiver to whole-genome samples of Hepatitis C Virus and Respiratory Syncytial Virus. shiver is publicly available from
  • Amele, S; Peters, L; Rodger, A; Lundgren, J; Rockstroh, J; Matulionyte, R; Leen, C; Jablonowska, E; Ostergaard, L; Bhagani, S; Sarcletti, M; Clarke, A; Falconer, K; Wandeler, G; Domingo, P; Maltez, F; Zaccarelli, M; Chkhartisvili, N; Szlavik, J; Stephan, C; Fonquernie, L; Aho, I; Mocroft, A; Group, ES (2021)
    Objectives: To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe. Methods: All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with >= 12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result >= 12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12. Results: 1042 individuals started interferon-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, and 789 [91.5%, 95% confidence interval (CI): 89.7 to 93.4] of which achieved SVR12. There were no differences in SVR12 across regions of Europe (P = 0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir +/- ribavirin (RBV) [adjusted odds ratio 0.21 (95% CI: 0.08 to 0.53)] or ombitasvir/paritaprevir/dasabuvir +/- RBV [adjusted odds ratio 0.46 (95% CI: 0.22 to 1.00)] compared with sofosbuvir/ledipasvir +/- RBV. Forty-three (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly because of toxicity (n = 14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n = 15.3%) and was related to treatment with atazanavir and ribavirin. Conclusions: Our findings from real-world data on HIV/HCV coinfected individuals across Europe show DAA treatment is well tolerated and that high rates of SVR12 can be achieved in all regions of Europe.
  • Lee, J-H.; Ostalecki, C.; Zhao, Z.; Kesti, T.; Bruns, H.; Simon, B.; Harrer, T.; Saksela, K.; Baur, A. S. (2018)
    HIV-Nef activates the myeloid cell-typical tyrosine kinase Hck, but its molecular role in the viral life cycle is not entirely understood. We found that HIV plasma extracellular vesicles (HIV pEV) containing/10 proteases and Nef also harbor Hck, and analyzed its role in the context of HIV pEV secretion. Myeloid cells required Hck for the vesicle-associated release of ADAM17. This could be induced by the introduction of Nef and implied that HIV targeted Hck for vesicle-associated ADAM17 secretion from a myeloid compartment. The other contents of HIV-pEV, however, including miRNA and effector protein profiles, as well as the presence of haptoglobin suggested hepatocytes as a possible cellular source. HIV liver tissue analysis supported this assumption, revealing induction of Hck translation, evidence for ADAMprotease activation and HIV infection. Our findings suggest that HIV targets Hck to induce pro-inflammatory vesicles release and identifies hepatocytes as a possible host cell compartment. (c) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
  • Vila-Real, Catarina; Pimenta-Martins, Ana; Gomes, Ana Maria; Pinto, Elisabete; Maina, Henry Ndegwa (2018)
    Background: Dietary patterns are often considered as one of the main causes of non-communicable diseases worldwide. It is of utmost importance to study dietary habits in developing countries since this work is scarce. Objective: To summarize the most recent research conducted in this field in African countries, namely the most used methodologies and tools. Methods: A systematic review was conducted on MEDLINE/PubMed, aiming to identify scientific publications focused on studies of dietary intake of different African populations, in a ten-year period. Papers not written in English/Portuguese/Spanish, studies developed among African people but not developed in African countries, studies aiming to assess a particular nutrient/specific food/food toxin and studies that assessed dietary intake among children were excluded. Findings: Out of 99 included studies, the 24-hour recall and the food-frequency questionnaire were the most used dietary intake assessment tools, used to assess diet at an individual level. It was also observed that often country-unspecific food composition databases are used, and the methodologies employed are poorly validated and standardized. Conclusions: There is an emergent need to improve the existing food databases by updating food data and to develop suitable country-specific databases for those that do not have their own food composition table.
  • Meuwissen, Pieter J.; Stolp, Bettina; Iannucci, Veronica; Vermeire, Jolien; Naessens, Evelien; Saksela, Kalle; Geyer, Matthias; Vanham, Guido; Arien, Kevin K.; Fackler, Oliver T.; Verhasselt, Bruno (2012)
  • Taube, Ran; Peterlin, Boris Matija (2013)
  • Taipale, Anni; Pelkonen, Tuula; Taipale, Marko; Roine, Irmeli; Bernardino, Luis; Peltola, Heikki; Pitkäranta, Anne (2011)