Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

Fourth report on chicken genes and chromosomes 2022

The chicken continues to hold its position as a leading model organism within many areas of research, as well as a being major source of protein for human consumption. The First Report on Chicken Genes and Chromosomes [Schmid et al., 2000], which was published in 2000, was the brainchild of the late, and sadly missed, Prof Michael Schmid of the University of Würzburg. It was a publication bringing together updates on the latest research and resources in chicken genomics and cytogenetics. The success of this First report led to the subsequent publication of the Second [Schmid et al., 2005] and Third [Schmid et al., 2015] reports proving popular references for the research community. It is now our pleasure to be able to introduce publication of the Fourth report. Being seven years since the last report, this publication captures the many advances that have taken place during that time. This includes presentation of the detailed genomic resources that are now available, largely due to increasing capabilities of sequencing technologies and which herald the pangenomic age, allowing for a much richer and more complete knowledge of the avian genome. Ongoing cytogenetic work also allows for examination of chromosomes, specific elements within chromosomes and the evolutionary history and comparison of karyotypes. We also examine chicken research efforts with a much more ‘global’ outlook with a greater impact on food security and the impact of climate change, and highlight the efforts of international consortia, such as the Chicken Diversity Consortium. We dedicate this Report to Michael