498 research outputs found
Structures of the Compact Helical Core Domains of Feline Calicivirus and Murine Norovirus VPg Proteins
Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of translation initiation factors
Noroviruses produce viral RNAs lacking a 5' cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyse changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex. The suppression of host ISG translation correlates with the activity of the viral protease (NS6) and the activation of cellular caspases leading to the establishment of an apoptotic environment. These results indicate that noroviruses exploit the differences between viral VPg-dependent and cellular cap-dependent translation in order to diminish the host response to infection.This work was supported by grants from the Wellcome Trust (097997/Z/11/Z, 101602/Z/13/Z) and BBSRC (Refs: BB/N001176/1 and BB/K002465/1) to IG, and an equipment grant to KH, IG (and others) from the Wellcome Trust (104914/Z/14/Z). RL is supported by a grant from the National Institutes for Health of the United States of America (AI50237). NL is supported by a BBSRC grant (BB/I01232X/1). IG is a Wellcome Senior Fellow. This work was also supported by the Intramural Research Program of the NIH, NIAID
First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon
We report the first measurement of coherent elastic neutrino-nucleus
scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge
National Laboratory Spallation Neutron Source. Two independent analyses prefer
\cevns over the background-only null hypothesis with greater than
significance. The measured cross section, averaged over the incident neutrino
flux, is (2.2 0.7) 10 cm -- consistent with the
standard model prediction. The neutron-number dependence of this result,
together with that from our previous measurement on CsI, confirms the existence
of the \cevns process and provides improved constraints on non-standard
neutrino interactions.Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3:
fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6:
fix Eq 1, new fig 3, V7 final version, updated with final revision
Observation of Coherent Elastic Neutrino-Nucleus Scattering
The coherent elastic scattering of neutrinos off nuclei has eluded detection
for four decades, even though its predicted cross-section is the largest by far
of all low-energy neutrino couplings. This mode of interaction provides new
opportunities to study neutrino properties, and leads to a miniaturization of
detector size, with potential technological applications. We observe this
process at a 6.7-sigma confidence level, using a low-background, 14.6-kg
CsI[Na] scintillator exposed to the neutrino emissions from the Spallation
Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic
signatures in energy and time, predicted by the Standard Model for this
process, are observed in high signal-to-background conditions. Improved
constraints on non-standard neutrino interactions with quarks are derived from
this initial dataset
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