title: Lassa virus nucleoprotein mutants generated by reverse genetics induce a robust type I interferon response in human dendritic cells and macrophages.
abstract: Lassa virus (LASV; Arenaviridae) is responsible for severe hemorrhagic fevers in Africa. LASV nucleoprotein (NP) plays important roles in regulating viral transcription and replication and in inhibiting type I interferon (IFN) production. The NP C-terminal domain contains a 3'-to-5' exonuclease activity involved in suppressing IFN induction. We have established a murine polymerase (Pol) I reverse genetics system for LASV, showing that residues D389 and G392 of NP were critical for LASV viability, while the D389A/G392A and D389T/392A double mutants were severely altered in the ability to suppress IFN in macrophages and dendritic cells. Assessing their attenuation in vivo may open new perspectives in vaccinology.
authors: Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France.
authors: Xavier
authors: X
authors: Carnec
authors: Sylvain
authors: S
authors: Baize
authors: Stéphanie
authors: S
authors: Reynard
authors: Laure
authors: L
authors: Diancourt
authors: Valérie
authors: V
authors: Caro
authors: Noel
authors: N
authors: Tordo
authors: Michèle
authors: M
authors: Bouloy
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology*; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D007370:Interferon Type I / Q000378:metabolism*; D007836:Lassa virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D014709:Vero Cells; D019562:Viral Load; D010948:Viral Plaque Assay
chemical_list: D036022:Capsid Proteins; D007370:Interferon Type I; D050505:Mutant Proteins; C110151:nucleocapsid protein, lassa virus