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Measuring Alphavirus Fidelity Using Non-Infectious Virus Particles.
Patterson, Edward I; Khanipov, Kamil; Swetnam, Daniele M; Walsdorf, Samantha; Kautz, Tiffany F; Thangamani, Saravanan; Fofanov, Yuriy; Forrester, Naomi L.
Afiliación
  • Patterson EI; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Khanipov K; Centre for Neglected Tropical Diseases, Departments of Vector Biology and Tropical Disease Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
  • Swetnam DM; Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Walsdorf S; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Kautz TF; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Thangamani S; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Fofanov Y; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Forrester NL; Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Viruses ; 12(5)2020 05 15.
Article en En | MEDLINE | ID: mdl-32429270
Mutations are incorporated into the genomes of RNA viruses at an optimal frequency and altering this precise frequency has been proposed as a strategy to create live-attenuated vaccines. However, determining the effect of specific mutations that alter fidelity has been difficult because of the rapid selection of the virus population during replication. By deleting residues of the structural polyprotein PE2 cleavage site, E3D56-59, in Venezuelan equine encephalitis virus (VEEV) TC-83 vaccine strain, non-infectious virus particles were used to assess the effect of single mutations on mutation frequency without the interference of selection that results from multiple replication cycles. Next-generation sequencing analysis revealed a significantly lower frequency of transversion mutations and overall mutation frequency for the fidelity mutants compared to VEEV TC-83 E3D56-59. We demonstrate that deletion of the PE2 cleavage site halts virus infection while making the virus particles available for downstream sequencing. The conservation of the site will allow the evaluation of suspected fidelity mutants across alphaviruses of medical importance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virión / Replicación Viral / Alphavirus / Mutación Límite: Animals Idioma: En Revista: Viruses Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virión / Replicación Viral / Alphavirus / Mutación Límite: Animals Idioma: En Revista: Viruses Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza