title: A substitution in the transmembrane region of the glycoprotein leads to an unstable attenuation of Machupo virus.
abstract: Machupo virus (MACV) is the etiologic agent of Bolivian hemorrhagic fever (BHF). Utilizing a reverse-genetics system recently developed, we report the rescue of a rationally modified recombinant MACV containing a single mutation in the transmembrane region of the glycoprotein. Following challenge of susceptible mice, we identified a significant reduction in virulence in the novel virus. We also identified an instability leading to reversion of the single mutation to a wild-type genotype.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Patterson
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Koma
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Alexey
authors.initials: A
authors.lastname: Seregin
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Milagros
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Yun
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Jeanon
authors.initials: J
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA slpaessl@utmb.edu.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D006477:Arenaviruses, New World / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D001483:Base Sequence; D002462:Cell Membrane / Q000821:virology*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006478:Hemorrhagic Fever, American / Q000821:virology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
chemical_list: D006023:Glycoproteins; D014764:Viral Proteins