title: Adaptation of yellow fever virus 17D to Vero cells is associated with mutations in structural and non-structural protein genes.
abstract: Serial passaging of yellow fever virus 17D in Vero cells was employed to derive seed material for a novel inactivated vaccine, XRX-001. Two independent passaging series identified a novel lysine to arginine mutation at amino acid 160 of the envelope protein, a surface-exposed residue in structural domain I. A third passage series resulted in an isoleucine to methionine mutation at residue 113 of the NS4B protein, a central membrane spanning region of the protein which has previously been associated with Vero cell adaptation of other mosquito-borne flaviviruses. These studies confirm that flavivirus adaptation to growth in Vero cells can be mediated by structural or non-structural protein mutations.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA. d.beasley@utmb.edu
authors.forename: David W C
authors.initials: DW
authors.lastname: Beasley
authors.forename: Merribeth
authors.initials: M
authors.lastname: Morin
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Lamb
authors.forename: Edward
authors.initials: E
authors.lastname: Hayman
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Watts
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Lee
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Trent
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution; D000818:Animals; D002522:Chlorocebus aethiops; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011487:Protein Conformation; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*; D015005:Yellow fever virus / Q000235:genetics* / Q000254:growth & development*
chemical_list: D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins
keywords: Vaccine; Vero cells; Yellow fever virus