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      Molecular Features of the Measles Virus Viral Fusion Complex That Favor Infection and Spread in the Brain

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          ABSTRACT

          Measles virus (MeV) bearing a single amino acid change in the fusion protein (F)—L454W—was isolated from two patients who died of MeV central nervous system (CNS) infection. This mutation in F confers an advantage over wild-type virus in the CNS, contributing to disease in these patients. Using murine ex vivo organotypic brain cultures and human induced pluripotent stem cell-derived brain organoids, we show that CNS adaptive mutations in F enhance the spread of virus ex vivo. The spread of virus in human brain organoids is blocked by an inhibitory peptide that targets F, confirming that dissemination in the brain tissue is attributable to F. A single mutation in MeV F thus alters the fusion complex to render MeV more neuropathogenic.

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          Most cited references79

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            Trimmomatic: a flexible trimmer for Illumina sequence data

            Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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              Fast gapped-read alignment with Bowtie 2.

              As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
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                Author and article information

                Contributors
                Role: Invited Editor
                Role: Editor
                Journal
                mBio
                mBio
                mbio
                mbio
                mBio
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                1 June 2021
                May-Jun 2021
                1 June 2021
                : 12
                : 3
                : e00799-21
                Affiliations
                [a ]Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
                [b ]Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
                [c ]CIRI, Centre International de Recherche en Infectiologie, Team Immuno-Biology of Viral Infections, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France
                [d ]Department of Experimental Medicine, University of Study of Campania “Luigi Vanvitelli”, Naples, Italy
                [e ]Department of Laboratory Medicine, University of Washington Medical Center, Seattle, Washington, USA
                [f ]Stem Cell Core Facility, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
                [g ]Department of Chemistry, University of Wisconsin–Madison, Madison, Wisconsin, USA
                [h ]Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA
                [i ]Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
                [j ]Division of Medical Virology, Department of Clinical Laboratory Sciences, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa
                [k ]Department of Microbiology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
                [l ]Department of Physiology and Cellular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
                University of Pittsburgh School of Medicine
                Washington University School of Medicine
                Author information
                https://orcid.org/0000-0002-6682-2029
                https://orcid.org/0000-0001-7054-4204
                https://orcid.org/0000-0003-0578-7765
                https://orcid.org/0000-0003-3866-9220
                Article
                mBio00799-21
                10.1128/mBio.00799-21
                8263006
                34061592
                2e2f7847-9b43-4a8b-8de0-a2b94058fb17
                Copyright © 2021 Mathieu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 23 March 2021
                : 23 April 2021
                Page count
                supplementary-material: 9, Figures: 4, Tables: 2, Equations: 0, References: 79, Pages: 19, Words: 13682
                Funding
                Funded by: HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID), FundRef https://doi.org/10.13039/100000060;
                Award ID: AI121349
                Award Recipient :
                Funded by: HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS), FundRef https://doi.org/10.13039/100000065;
                Award ID: NS091263
                Award Recipient :
                Funded by: HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS), FundRef https://doi.org/10.13039/100000065;
                Award ID: NS105699
                Award Recipient :
                Funded by: HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID), FundRef https://doi.org/10.13039/100000060;
                Award ID: AI146980
                Award Recipient :
                Funded by: Agence Nationale de la Recherche (ANR), FundRef https://doi.org/10.13039/501100001665;
                Award ID: ANR-13-PDOC-0010-01
                Award Recipient :
                Funded by: Agence Nationale de la Recherche (ANR), FundRef https://doi.org/10.13039/501100001665;
                Award ID: ANR-11-LABX-0048
                Award Recipient :
                Funded by: Agence Nationale de la Recherche (ANR), FundRef https://doi.org/10.13039/501100001665;
                Award ID: ANR-11-IDEX-0007
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                May/June 2021

                Life sciences
                viral fusion,central nervous system infection,host-pathogen interaction,viral evolution

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