title: The major determinant of attenuation in mice of the Candid1 vaccine for Argentine hemorrhagic fever is located in the G2 glycoprotein transmembrane domain.
abstract: Candid1, a live-attenuated Junin virus vaccine strain, was developed during the early 1980s to control Argentine hemorrhagic fever, a severe and frequently fatal human disease. Six amino acid substitutions were found to be unique to this vaccine strain, and their role in virulence attenuation in mice was analyzed using a series of recombinant viruses. Our results indicate that Candid1 is attenuated in mice through a single amino acid substitution in the transmembrane domain of the G2 glycoprotein. This work provides insight into the molecular mechanisms of attenuation of the only arenavirus vaccine currently available.
authors.affiliation: Centers for Disease Control and Prevention, MS G14, Atlanta, GA 30329, USA. bwu4@cdc.gov
authors.forename: César G
authors.initials: CG
authors.lastname: Albariño
authors.forename: Brian H
authors.initials: BH
authors.lastname: Bird
authors.forename: Ayan K
authors.initials: AK
authors.lastname: Chakrabarti
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Dodd
authors.forename: Mike
authors.initials: M
authors.lastname: Flint
authors.forename: Eric
authors.initials: E
authors.lastname: Bergeron
authors.forename: David M
authors.initials: DM
authors.lastname: White
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001117:Arenaviridae Infections / Q000473:pathology / Q000821:virology; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D018051:Junin virus / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017354:Point Mutation; D012376:Rodent Diseases / Q000473:pathology / Q000821:virology; D017422:Sequence Analysis, DNA; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D037521:Virulence Factors