title: Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion.
abstract: Fifteen mutant dengue viruses were engineered and used to identify AAs in the molecular hinge of the envelope protein that are critical to viral infection. Substitutions at Q52, A54, or E133 reduced infectivity in mammalian cells and altered the pH threshold of fusion. Mutations at F193, G266, I270, or G281 affected viral replication in mammalian and mosquito cells, but only I270W had reduced fusion activity. T280Y affected the pH threshold for fusion and reduced replication in C6/36 cells. Three different mutations at L135 were lethal in mammalian cells. Among them, L135G abrogated fusion and reduced replication in C6/36 cells, but only slightly reduced the mosquito infection rate. Conversely, L135W replicated well in C6/36 cells, but had the lowest mosquito infection rate. Possible interactions between hinge residues 52 and 277, or among 53, 135, 170, 186, 265, and 276 required for hinge function were discovered by sequence analysis to identify compensatory mutations.
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.
authors.forename: Siritorn
authors.initials: S
authors.lastname: Butrapet
authors.forename: Thomas
authors.initials: T
authors.lastname: Childers
authors.forename: Kelley J
authors.initials: KJ
authors.lastname: Moss
authors.forename: Steven M
authors.initials: SM
authors.lastname: Erb
authors.forename: Betty E
authors.initials: BE
authors.lastname: Luy
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Calvert
authors.forename: Carol D
authors.initials: CD
authors.lastname: Blair
authors.forename: John T
authors.initials: JT
authors.lastname: Roehrig
authors.forename: Claire Y-H
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000330:Aedes; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D003715:Dengue / Q000821:virology*; D003716:Dengue Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins