The Structure of a Conserved Piezo Channel Domain Reveals a Topologically Distinct β Sandwich Fold
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Flaviviruses have evolved means to evade host innate immune responses. Recent evidence suggests this is due to prevention of interferon production and signaling in flavivirus-infected cells. Here we show that the interferon-induced MxA protein can sequester the West Nile virus strain Kunjin virus (WNV{sub KUN}) capsid protein in cytoplasmic tubular structures in an expression-replication system. This sequestering resulted in reduced titers of secreted WNV{sub KUN} particles. We show by electron microscopy, tomography and 3D modeling that these cytoplasmic tubular structures form organized bundles. Additionally we show that recombinant ER-targeted MxA can restrict production of infectious WNV{sub KUN} under conditions of virus infection. Our results indicate a co-ordinated and compartmentalized WNV{sub KUN} assembly process may prevent recognition of viral components by MxA, particularly the capsid protein. This recognition can be exploited if MxA is targeted to intracellular sites of WNV{sub KUN} assembly. This results in further understanding of the mechanisms of flavivirus evasion from the immune system. - Highlights: • We show that the ISG MxA can recognize the West Nile virus capsid protein. • Interaction between WNV C protein and MxA induces cytoplasmic fibrils. • MxA can be retargeted to the ER to restrict WNV particle release. • WNV assembly process is a strategy to avoid MxA recognition.
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We derive a Noether current for the Eulerian variational principle of ideal non-barotropic magnetohydrodynamics (MHD). It was shown previously that ideal non-barotropic MHD is mathematically equivalent to a five function field theory with an induced geometrical structure in the case that field lines cover surfaces and this theory can be described using a variational principle. Here we use various symmetries of the flow to derive topological constants of motion through the derived Noether current and discuss their implication for non-barotropic MHD.
Kinetic simulations of relativistic gases and plasmas are critical for understanding diverse astrophysical and terrestrial systems, but the accurate construction of the relativistic Maxwellian, the Maxwell–Jüttner distribution, on a discrete simulation grid is challenging. Difficulties arise from the finite velocity bounds of the domain, which may not capture the entire distribution function, as well as errors introduced by projecting the function onto a discrete grid. Here, we present a novel scheme for iteratively correcting the moments of the projected distribution applicable to all grid-based discretizations of the relativistic kinetic equation. In addition, we describe how to compute the needed nonlinear quantities, such as Lorentz boost factors, in a discontinuous Galerkin scheme through a combination of numerical quadrature and weak operations. The resulting method accurately captures the distribution function and ensures that the moments match the desired values to machine precision.
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Correction was made to the funding and acknowledgment: Funding V.-A.G. was supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division. R.R. and M.-T.N. were supported by the Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory (PNNL) CheMSR Agile Investment. PNNL is operated by DE-AC05-76RLO01830. J.-B.L. and J.L. were supported by the National Natural Science Foundation of China (Nos. 21433005, 91645203, and 21590792). D.C.C. was supported by Research and Innovation at the University of Nevada, Reno. ACKNOWLEDGMENTS The research was performed using resources available through Research Computing at Pacific Northwest National Laboratory (PNNL), Tsinghua National Laboratory for Information Science and Technology and the Computational Chemistry Laboratory under Tsinghua Xuetang Talents Program, and University of Nevada, Reno High Performance Computing. J.- B.L. and J.L. acknowledge discussions with Dr. Yang-Gang Wang (Southern University of Science and Technology).
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