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      Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation

      research-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 10 , 11 , 12 , 10 , 10 , 13 , 14 , 6 , 6 , 6 , 15 , 16 , 17 , 18 , 17 , 18 , 19 , 1 , 1 , 8 , 20 , 5 , 21 , 4 , 4 , 19 , 12 , 12 , 12 , 11 , 11 , 11 , 12 , 11 , 6 , 15 , The Genotype to Phenotype Japan (G2P-Japan) Consortium, 17 , 18 , , 13 , 14 , , 8 , , 5 , , 6 , 7 , 15 , , 10 , 14 ,
      Nature
      Nature Publishing Group UK
      SARS-CoV-2, Viral pathogenesis

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          Abstract

          During the current coronavirus disease 2019 (COVID-19) pandemic, a variety of mutations have accumulated in the viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, at the time of writing, four variants of concern are considered to be potentially hazardous to human society 1 . The recently emerged B.1.617.2/Delta variant of concern is closely associated with the COVID-19 surge that occurred in India in the spring of 2021 (ref. 2 ). However, the virological properties of B.1.617.2/Delta remain unclear. Here we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates cleavage of the spike protein and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity compared with its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.

          Abstract

          The P681R mutation in the spike protein renders the Delta variant more pathogenic than prototypic SARS-CoV-2 in infected hamsters, and facilitates spike protein cleavage and enhances viral fusogenicity.

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          Most cited references40

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          MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability

          We report a major update of the MAFFT multiple sequence alignment program. This version has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update. This report shows actual examples to explain how these features work, alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments, and our ongoing efforts to overcome such limitations.
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            fastp: an ultra-fast all-in-one FASTQ preprocessor

            Abstract Motivation Quality control and preprocessing of FASTQ files are essential to providing clean data for downstream analysis. Traditionally, a different tool is used for each operation, such as quality control, adapter trimming and quality filtering. These tools are often insufficiently fast as most are developed using high-level programming languages (e.g. Python and Java) and provide limited multi-threading support. Reading and loading data multiple times also renders preprocessing slow and I/O inefficient. Results We developed fastp as an ultra-fast FASTQ preprocessor with useful quality control and data-filtering features. It can perform quality control, adapter trimming, quality filtering, per-read quality pruning and many other operations with a single scan of the FASTQ data. This tool is developed in C++ and has multi-threading support. Based on our evaluation, fastp is 2–5 times faster than other FASTQ preprocessing tools such as Trimmomatic or Cutadapt despite performing far more operations than similar tools. Availability and implementation The open-source code and corresponding instructions are available at https://github.com/OpenGene/fastp.
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              IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era

              Abstract IQ-TREE (http://www.iqtree.org, last accessed February 6, 2020) is a user-friendly and widely used software package for phylogenetic inference using maximum likelihood. Since the release of version 1 in 2014, we have continuously expanded IQ-TREE to integrate a plethora of new models of sequence evolution and efficient computational approaches of phylogenetic inference to deal with genomic data. Here, we describe notable features of IQ-TREE version 2 and highlight the key advantages over other software.
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                Author and article information

                Contributors
                tanaka@med.hokudai.ac.jp
                so@tokai.ac.jp
                ikedat@kumamoto-u.ac.jp
                fukut@pop.med.hokudai.ac.jp
                yoshihiro.kawaoka@wisc.edu
                KeiSato@g.ecc.u-tokyo.ac.jp
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                25 November 2021
                25 November 2021
                2022
                : 602
                : 7896
                : 300-306
                Affiliations
                [1 ]GRID grid.410849.0, ISNI 0000 0001 0657 3887, Department of Veterinary Science, Faculty of Agriculture, , University of Miyazaki, ; Miyazaki, Japan
                [2 ]GRID grid.410849.0, ISNI 0000 0001 0657 3887, Center for Animal Disease Control, , University of Miyazaki, ; Miyazaki, Japan
                [3 ]GRID grid.410849.0, ISNI 0000 0001 0657 3887, Graduate School of Medicine and Veterinary Medicine, , University of Miyazaki, ; Miyazaki, Japan
                [4 ]GRID grid.257022.0, ISNI 0000 0000 8711 3200, Institute of Biomedical and Health Sciences, , Hiroshima University, ; Hiroshima, Japan
                [5 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Department of Microbiology and Immunology, Graduate School of Medicine, , Hokkaido University, ; Hokkaido, Japan
                [6 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Division of Virology, Institute of Medical Science, , University of Tokyo, ; Tokyo, Japan
                [7 ]GRID grid.14003.36, ISNI 0000 0001 2167 3675, Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, , University of Wisconsin-Madison, ; Madison, WI USA
                [8 ]GRID grid.274841.c, ISNI 0000 0001 0660 6749, Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, , Kumamoto University, ; Kumamoto, Japan
                [9 ]GRID grid.33003.33, ISNI 0000 0000 9889 5690, Department of Clinical Pathology, Faculty of Medicine, , Suez Canal University, ; Ismailia, Egypt
                [10 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Division of Systems Virology, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, , The University of Tokyo, ; Tokyo, Japan
                [11 ]GRID grid.258799.8, ISNI 0000 0004 0372 2033, Department of Hematology and Oncology, Graduate School of Medicine, , Kyoto University, ; Kyoto, Japan
                [12 ]GRID grid.417096.d, Tokyo Metropolitan Institute of Public Health, ; Tokyo, Japan
                [13 ]GRID grid.265061.6, ISNI 0000 0001 1516 6626, Department of Molecular Life Science, , Tokai University School of Medicine, ; Kanagawa, Japan
                [14 ]GRID grid.419082.6, ISNI 0000 0004 1754 9200, CREST, Japan Science and Technology Agency, ; Saitama, Japan
                [15 ]GRID grid.45203.30, ISNI 0000 0004 0489 0290, The Research Center for Global Viral Diseases, , National Center for Global Health and Medicine Research Institute, ; Tokyo, Japan
                [16 ]GRID grid.28803.31, ISNI 0000 0001 0701 8607, Department of Surgical Sciences, School of Veterinary Medicine, , University of Wisconsin, ; Madison, WI USA
                [17 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Department of Cancer Pathology, Faculty of Medicine, , Hokkaido University, ; Hokkaido, Japan
                [18 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), , Hokkaido University, ; Hokkaido, Japan
                [19 ]GRID grid.410795.e, ISNI 0000 0001 2220 1880, Department of Pathology, , National Institute of Infectious Diseases, ; Tokyo, Japan
                [20 ]GRID grid.274841.c, ISNI 0000 0001 0660 6749, Graduate School of Medical Sciences, , Kumamoto University, ; Kumamoto, Japan
                [21 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Institute for Genetic Medicine, , Hokkaido University, ; Hokkaido, Japan
                Author information
                http://orcid.org/0000-0002-2792-4399
                http://orcid.org/0000-0003-3765-8482
                http://orcid.org/0000-0001-9163-1665
                http://orcid.org/0000-0002-7469-1276
                http://orcid.org/0000-0003-0541-706X
                http://orcid.org/0000-0003-0440-8321
                http://orcid.org/0000-0002-8266-020X
                http://orcid.org/0000-0001-7768-5157
                http://orcid.org/0000-0001-5400-5905
                http://orcid.org/0000-0001-6145-395X
                http://orcid.org/0000-0002-1764-2937
                http://orcid.org/0000-0002-7633-7238
                http://orcid.org/0000-0001-9866-4398
                http://orcid.org/0000-0002-3825-7018
                http://orcid.org/0000-0002-0062-2753
                http://orcid.org/0000-0002-3754-1252
                http://orcid.org/0000-0002-2625-5322
                http://orcid.org/0000-0002-2572-6786
                http://orcid.org/0000-0001-8069-9250
                http://orcid.org/0000-0002-1046-8286
                http://orcid.org/0000-0001-7678-4284
                http://orcid.org/0000-0001-6470-3301
                http://orcid.org/0000-0003-1760-3839
                http://orcid.org/0000-0003-2869-9450
                http://orcid.org/0000-0001-5471-8331
                http://orcid.org/0000-0001-5061-8296
                http://orcid.org/0000-0003-4431-1380
                Article
                4266
                10.1038/s41586-021-04266-9
                8828475
                34823256
                d27b3df2-def7-4471-8f2d-f57a6a924ff1
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 July 2021
                : 18 November 2021
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                sars-cov-2,viral pathogenesis
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                sars-cov-2, viral pathogenesis

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