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      Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement

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          Abstract

          Influenza viruses replicate within the nucleus of the host cell. This uncommon RNA virus trait provides influenza with the advantage of access to the nuclear machinery during replication. However, it also increases the complexity of the intracellular trafficking that is required for the viral components to establish a productive infection. The segmentation of the influenza genome makes these additional trafficking requirements especially challenging, as each viral RNA (vRNA) gene segment must navigate the network of cellular membrane barriers during the processes of entry and assembly. To accomplish this goal, influenza A viruses (IAVs) utilize a combination of viral and cellular mechanisms to coordinate the transport of their proteins and the eight vRNA gene segments in and out of the cell. The aim of this review is to present the current mechanistic understanding for how IAVs facilitate cell entry, replication, virion assembly, and intercellular movement, in an effort to highlight some of the unanswered questions regarding the coordination of the IAV infection process.

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          Most cited references261

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          A census of human RNA-binding proteins.

          Post-transcriptional gene regulation (PTGR) concerns processes involved in the maturation, transport, stability and translation of coding and non-coding RNAs. RNA-binding proteins (RBPs) and ribonucleoproteins coordinate RNA processing and PTGR. The introduction of large-scale quantitative methods, such as next-generation sequencing and modern protein mass spectrometry, has renewed interest in the investigation of PTGR and the protein factors involved at a systems-biology level. Here, we present a census of 1,542 manually curated RBPs that we have analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression. Our analysis is a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.
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            Lipid rafts as a membrane-organizing principle.

            Cell membranes display a tremendous complexity of lipids and proteins designed to perform the functions cells require. To coordinate these functions, the membrane is able to laterally segregate its constituents. This capability is based on dynamic liquid-liquid immiscibility and underlies the raft concept of membrane subcompartmentalization. Lipid rafts are fluctuating nanoscale assemblies of sphingolipid, cholesterol, and proteins that can be stabilized to coalesce, forming platforms that function in membrane signaling and trafficking. Here we review the evidence for how this principle combines the potential for sphingolipid-cholesterol self-assembly with protein specificity to selectively focus membrane bioactivity.
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              Viral membrane fusion.

              Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a "fusion loop" or "fusion peptide") engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                20 July 2018
                2018
                : 9
                : 1581
                Affiliations
                Department of Biochemistry and Biophysics, Stockholm University , Stockholm, Sweden
                Author notes

                Edited by: Alan Chen-Yu Hsu, University of Newcastle, Australia

                Reviewed by: Bernard A. P. Lafont, National Institute of Allergy and Infectious Diseases (NIAID), United States; Alan G. Goodman, Washington State University, United States; Julie McAuley, University of Melbourne, Australia

                *Correspondence: Robert Daniels, robertd@ 123456dbb.su.se

                Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.01581
                6062596
                30079062
                cdf7210d-117a-4f55-8fbc-0799a6cd8bc8
                Copyright © 2018 Dou, Revol, Östbye, Wang and Daniels.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 April 2018
                : 26 June 2018
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 249, Pages: 17, Words: 15343
                Funding
                Funded by: Carl Tryggers Stiftelse för Vetenskaplig Forskning 10.13039/501100002805
                Award ID: CTS17:111
                Funded by: Vetenskapsrådet 10.13039/501100004359
                Award ID: K2015-57-21980-04-4
                Categories
                Immunology
                Review

                Immunology
                influenza a virus,viral ribonucleoprotein,hemagglutinin,viral entry mechanism,viral envelope proteins,ha and na,viral replication,neuraminidase

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