Multicenter performance evaluation of the Elecsys HCV Duo immunoassay.

BACKGROUND: The diagnostic accuracy of the Elecsys® HCV Duo antigen-antibody combination immunoassay (Roche Diagnostics GmbH) was evaluated for the detection of hepatitis C virus (HCV) infection, versus commercially available comparators. METHODS: This multicenter study (August 2020-March 2021) assessed the specificity of the Elecsys HCV Duo immunoassay and comparator assays in blood donor and routine clinical laboratory samples; sensitivity was determined in confirmed HCV-positive samples and seroconversion panels. The Elecsys HCV Duo immunoassay was compared with the Monolisa HCV Ag-Ab ULTRA V2, Murex HCV Ag/Ab Combination and ARCHITECT HCV Ag assays, as well as nucleic acid testing (NAT). The antibody (anti-HCV) module of the Elecsys HCV Duo immunoassay was compared with the Elecsys Anti-HCV II, Alinity s Anti-HCV, ARCHITECT Anti-HCV and RIBA HCV 3.0 SIA assays. RESULTS: The specificity of the Elecsys HCV Duo immunoassay was 99.94% (95% confidence interval [CI], 99.89-99.97) and 99.92% (95% CI, 99.71-99.99) in blood donor (n = 20,634) and routine clinical laboratory samples (n = 2531), respectively. The specificity of the Elecsys HCV Duo immunoassay was similar or better than comparator assays. The sensitivity of the Elecsys HCV Duo immunoassay in confirmed HCV-positive samples (n = 257) was 99.6%. In seroconversion panels, the Elecsys HCV Duo immunoassay detected infections earlier (2.2-21.9 days) than all but one of the comparator assays and detected HCV 1.8 days later than NAT. CONCLUSIONS: The Elecsys HCV Duo immunoassay shows high diagnostic accuracy, reduces the diagnostic window, and could be used when NAT is not possible.

CopR, a Global Regulator of Transcription to Maintain Copper Homeostasis in Pyrococcus furiosus.

Although copper is in many cases an essential micronutrient for cellular life, higher concentrations are toxic. Therefore, all living cells have developed strategies to maintain copper homeostasis. In this manuscript, we have analyzed the transcriptome-wide response of Pyrococcus furiosus to increased copper concentrations and described the essential role of the putative copper-sensing metalloregulator CopR in the detoxification process. To this end, we employed biochemical and biophysical methods to characterize the role of CopR. Additionally, a copR knockout strain revealed an amplified sensitivity in comparison to the parental strain towards increased copper levels, which designates an essential role of CopR for copper homeostasis. To learn more about the CopR-regulated gene network, we performed differential gene expression and ChIP-seq analysis under normal and 20 µM copper-shock conditions. By integrating the transcriptome and genome-wide binding data, we found that CopR binds to the upstream regions of many copper-induced genes. Negative-stain transmission electron microscopy and 2D class averaging revealed an octameric assembly formed from a tetramer of dimers for CopR, similar to published crystal structures from the Lrp family. In conclusion, we propose a model for CopR-regulated transcription and highlight the regulatory network that enables Pyrococcus to respond to increased copper concentrations.