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Variant mutation in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation.
Kubinski, Hannah C; Despres, Hannah W; Johnson, Bryan A; Schmidt, Madaline M; Jaffrani, Sara A; Mills, Margaret G; Lokugamage, Kumari; Dumas, Caroline M; Shirley, David J; Estes, Leah K; Pekosz, Andrew; Crothers, Jessica W; Roychoudhury, Pavitra; Greninger, Alexander L; Jerome, Keith R; Di Genova, Bruno Martorelli; Walker, David H; Ballif, Bryan A; Ladinsky, Mark S; Bjorkman, Pamela J; Menachery, Vineet D; Bruce, Emily A.
Afiliación
  • Kubinski HC; Department of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington VT, 05405, USA.
  • Despres HW; Department of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington VT, 05405, USA.
  • Johnson BA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Schmidt MM; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
  • Jaffrani SA; Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX, USA.
  • Mills MG; Department of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington VT, 05405, USA.
  • Lokugamage K; Department of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington VT, 05405, USA.
  • Dumas CM; Virology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle WA 98195, USA.
  • Shirley DJ; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Estes LK; Department of Biology, University of Vermont 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington VT 05404, USA.
  • Pekosz A; Faraday, Inc. Data Science Department. Burlington VT, 05405, USA.
  • Crothers JW; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Roychoudhury P; W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Greninger AL; Department of Pathology and Laboratory Medicine, Robert Larner, MD College of Medicine, University of Vermont, Burlington, VT, USA.
  • Jerome KR; Virology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle WA 98195, USA.
  • Di Genova BM; Virology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle WA 98195, USA.
  • Walker DH; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA.
  • Ballif BA; Virology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle WA 98195, USA.
  • Ladinsky MS; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA.
  • Bjorkman PJ; Department of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington VT, 05405, USA.
  • Menachery VD; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Bruce EA; Department of Biology, University of Vermont 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington VT 05404, USA.
bioRxiv ; 2024 Mar 11.
Article en En | MEDLINE | ID: mdl-38559000
ABSTRACT
The evolution of SARS-CoV-2 variants and their respective phenotypes represents an important set of tools to understand basic coronavirus biology as well as the public health implications of individual mutations in variants of concern. While mutations outside of Spike are not well studied, the entire viral genome is undergoing evolutionary selection, particularly the central disordered linker region of the nucleocapsid (N) protein. Here, we identify a mutation (G215C), characteristic of the Delta variant, that introduces a novel cysteine into this linker domain, which results in the formation of a disulfide bond and a stable N-N dimer. Using reverse genetics, we determined that this cysteine residue is necessary and sufficient for stable dimer formation in a WA1 SARS-CoV-2 background, where it results in significantly increased viral growth both in vitro and in vivo. Finally, we demonstrate that the NG215C virus packages more nucleocapsid per virion and that individual virions are larger, with elongated morphologies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos