Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals

HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization

Functional and immunogenic characterization of diverse HCV glycoprotein E2 variants

© 2018 European Association for the Study of the Liver Background & Aims: Induction of cross-reactive antibodies targeting conserved epitopes of the envelope proteins E1E2 is a key requirement for an hepatitis C virus vaccine. Conserved epitopes like the viral CD81-binding site are targeted by rare broadly neutralizing antibodies. However, these viral segments are occluded by variable regions and glycans. We aimed to identify antigens exposing conserved epitopes and to characterize their immunogenicity. Methods: We created hepatitis C virus variants with mutated glycosylation sites and/or hypervariable region 1 (HVR1). Exposure of the CD81 binding site and conserved epitopes was quantified by soluble CD81 and antibody interaction and neutralization assays. E2 or E1-E2 heterodimers with mutations causing epitope exposure were used to immunize mice. Vaccine-induced antibodies were examined and compared with patient-derived antibodies. Results: Mutant viruses bound soluble CD81 and antibodies targeting the CD81 binding site with enhanced efficacy. Mice immunized with E2 or E1E2 heterodimers incorporating these modifications mounted strong, cross-binding, and non-interfering antibodies. E2-induced antibodies neutralized the autologous virus but they were not cross-neutralizing. Conclusions: Viruses lacking the HVR1 and selected glycosylation sites expose the CD81 binding site and cross-neutralization antibody epitopes. Recombinant E2 proteins carrying these modifications induce strong cross-binding but not cross-neutralizing antibodies. Lay summary: Conserved viral epitopes can be made considerably more accessible for binding of potently neutralizing antibodies by deletion of hypervariable region 1 and selected glycosylation sites. Recombinant E2 proteins carrying these mutations are unable to elicit cross-neutralizing antibodies suggesting that exposure of conserved epitopes is not sufficient to focus antibody responses on production of cross-neutralizing antibodies

Texturuntersuchungen an Gesteinen mittels Neutronenstrahlbeugung (speziell an Halit, Quarz und Galenit) Zwischenbericht

Texture analyses by neutron diffraction were carried out on the minerals halite (deposits Zielitz and Merkers), galenite (deposit Lauterberg) and quartz (Reitzenhain structure, Erzgebirge). The influence of tectonics, lithostatic pressure and recrystallization on the distribution of crystallite orientation (texture) was studied on the halite (NaCl) samples. While samples from the deposit Zielitz exhibit an isotropic orientation distribution, samples from Merkers exhibit a (100) - fiber texture. In deformation experiments the conversion to a (100) - fiber texture was observed. The case of fabric isotropization under granitization was studied on two quartz samples. No reference to relictic texture properties due to earlier deformation phases could be found. While one of the quartz samples proved to be exturally isotropic, the other sample showed a slightly preferred orientation of the quartz axes which correlate with a local tectonic disturbance. (WEN)SIGLEAvailable from TIB Hannover: RR 6134(95/19)+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Synthesis of β-Ketoiminato Copper(II) Complexes and their Use in Copper Deposition

The template synthesis of ethylenediamine (1 ) with 2‐acetylcyclopentanone (2 ) and [Cu(OAc)2· H2O] (5 ) produced [Cu(1‐(2‐c C5H6(O))C(Me)NCH2)2)] (6 ) in 82 % yield. Reaction of 5 with bis(benzoylacetone)diethylenetriamine (7 , = L H)[1] gave [Cu(μ‐OAc)(L )(H2O)]2 (8 ). The solid‐state structures of 6 and 8 were determined confirming that 8 possesses intra‐ and intermolecular hydrogen bonds resulting in a dimer formation. The thermal behavior of 6 –8 was studied by TG and TG‐MS. Under oxygen CuO was formed, whereas under Ar Cu/Cu2O (6 ) or Cu (8 ) was obtained. Complex 6 was used as CVD precursor for Cu and Cu‐oxide deposition (substrate temp., 400–500 °C, N2, 60 mL· min–1; O2, 60 mL· min–1; pressure, 0.87–1.5 mbar). The as‐obtained deposits show separated particles of different appearance at the substrate surface as evidenced by SEM. Non ‐volatile 8 was applied as spin‐coating precursor for Cu and CuO formation [conc. 0.25 mol· L–1; volume 0.2 mL; 3000 rpm; depos. time 2 min; heating rate 50 K· min–1; holding time 60 min (Ar), 120 min (air) at 800 °C]. The samples on silicon consist of granulated particles (Ar) or are non‐dense with a grainy topography (air). EDX and XPS measurements confirmed the formation of Cu (Ar) or CuO (O2) with up to 13 mol‐% C impurity