SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses.

The human interferon (IFN)-induced MxA protein is a key antiviral host restriction factor exhibiting broad antiviral activity against many RNA viruses, including highly pathogenic avian influenza A viruses (IAV) of the H5N1 and H7N7 subtype. To date the mechanism for how MxA exerts its antiviral activity is unclear, however, additional cellular factors are believed to be essential for this activity. To identify MxA cofactors we performed a genome-wide siRNA-based screen in human airway epithelial cells (A549) constitutively expressing MxA using an H5N1 reporter virus. These data were complemented with a proteomic screen to identify MxA-interacting proteins. The combined data identified SMARCA2, the ATPase subunit of the BAF chromatin remodeling complex, as a crucial factor required for the antiviral activity of MxA against IAV. Intriguingly, our data demonstrate that although SMARCA2 is essential for expression of some IFN-stimulated genes (ISGs), and the establishment of an antiviral state, it is not required for expression of MxA, suggesting an indirect effect on MxA activity. Transcriptome analysis of SMARCA2-depleted A549-MxA cells identified a small set of SMARCA2-regulated factors required for activity of MxA, in particular IFITM2 and IGFBP3. These findings reveal that several virus-inducible factors work in concert to enable MxA restriction of IAV

Sensory and corticospinal signs before ataxia onset in SCA1 and SCA3: the READISCA study

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Author Correction: SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

Genomic reconstruction of the SARS-CoV-2 epidemic in England

AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p

Observation of the Λb0→χc1(3872)pK−\Lambda_b^0\rightarrow \chi_{c1}(3872)pK^- decay

International audienceUsing proton-proton collision data, collected with the LHCb detector and corresponding to 1.0, 2.0 and 1.9 fb$^{−1}$ of integrated luminosity at the centre-of-mass energies of 7, 8, and 13 TeV, respectively, the decay {\Lambda}_{\mathrm{b}}^0\to {\upchi}_{\mathrm{c}1} (3872)pK$^{−}$ with χ$_{c1}$(3872) → J/ψ π$^{+}$π$^{−}$ is observed for the first time. The significance of the observed signal is in excess of seven standard deviations. It is found that (58 ± 15)% of the decays proceed via the two-body intermediate state χ$_{c1}$(3872)Λ(1520). The branching fraction with respect to that of the ${\Lambda}_{\mathrm{b}}^0$ → ψ(2S)pK$^{−}$ decay mode, where the ψ(2S) meson is reconstructed in the J/ψ π$^{+}$π$^{−}$ final state, is measured to be: $ \frac{\beta \left({\Lambda}_{\mathrm{b}}^0\to {\upchi}_{\mathrm{c}1}(3872){\mathrm{pK}}^{-}\right)}{\beta \left({\Lambda}_{\mathrm{b}}^0\to \uppsi \left(2\mathrm{S}\right){\mathrm{pK}}^{-}\right)}\times \frac{\beta \left({\upchi}_{\mathrm{c}1}(3872)\to \mathrm{J}/\uppsi {\uppi}^{+}{\uppi}^{-}\right)}{\beta \left(\uppsi \left(2\mathrm{S}\right)\to \mathrm{J}/\uppsi {\uppi}^{+}{\uppi}^{-}\right)}=\left(5.4\pm 1.1\pm 0.2\right)\times {10}^{-2},

Measurement of fs/fuf_s / f_u Variation with Proton-Proton Collision Energy and BB-Meson Kinematics

International audienceThe ratio of the Bs0 and B+ fragmentation fractions fs and fu is studied with Bs0→J/ψϕ and B+→J/ψK+ decays using data collected by the LHCb experiment in proton-proton collisions at 7, 8, and 13 TeV center-of-mass energies. The analysis is performed in bins of B-meson momentum, longitudinal momentum, transverse momentum, pseudorapidity, and rapidity. The fragmentation-fraction ratio fs/fu is observed to depend on the B-meson transverse momentum with a significance of 6.0σ. This dependency is driven by the 13 TeV sample (8.7σ), while the results for the other collision energies are not significant when considered separately. Furthermore, the results show a 4.8σ evidence for an increase of fs/fu as a function of collision energy

Updated measurement of time-dependent CP-violating observables in Bs0→J/ψK+K−B^{0}_{s}\to J/\psi K^+ K^- decays

International audienceThe decay-time-dependent $CP$ asymmetry in ${{B} ^0_{s}} \rightarrow J/\psi {{K} ^+} {{K} ^-}$ decays is measured using proton–proton collision data, corresponding to an integrated luminosity of $1.9\,\mathrm{fb}^{-1}$ , collected with the LHCb detector at a centre-of-mass energy of $13\,\mathrm {TeV}$ in 2015 and 2016. Using a sample of approximately 117 000 signal decays with an invariant ${{K} ^+} {{K} ^-}$ mass in the vicinity of the $\phi (1020)$ resonance, the $CP$ -violating phase $\phi _s$ is measured, along with the difference in decay widths of the light and heavy mass eigenstates of the ${{B} ^0_{s}}$ - ${{\overline{B}{}} {}^0_{s}}$ system, $\Delta \Gamma _s$ . The difference of the average ${{B} ^0_{s}}$ and ${{B} ^0}$ meson decay widths, $\Gamma _s-\Gamma _d$ , is determined using in addition a sample of ${{B} ^0} \rightarrow J/\psi {{K} ^+} {{\pi } ^-}$ decays. The values obtained are $\phi _s = -0.083\pm 0.041\pm 0.006\mathrm { \,rad}$ , $\Delta \Gamma _s = 0.077 \pm 0.008 \pm 0.003 {\mathrm { \,ps^{-1}}}$ and $\Gamma _s-\Gamma _d = -0.0041 \pm 0.0024 \pm 0.0015{\mathrm { \,ps^{-1}}}$ , where the first uncertainty is statistical and the second systematic. These are the most precise single measurements of these quantities to date and are consistent with expectations based on the Standard Model and with a previous LHCb analysis of this decay using data recorded at centre-of-mass energies 7 and 8 TeV. Finally, the results are combined with recent results from ${{B} ^0_{s}} \rightarrow J/\psi {{\pi } ^+} {{\pi } ^-}$ decays obtained using the same dataset as this analysis, and with previous independent LHCb results