反向遗传学生成的拉沙病毒核蛋白突变体能在人树突状细胞和巨噬细胞中诱导强烈的 I 型干扰素反应。
Lassa virus nucleoprotein mutants generated by reverse genetics induce a robust type I interferon response in human dendritic cells and macrophages.
机构信息
Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France.
出版信息
J Virol. 2011 Nov;85(22):12093-7. doi: 10.1128/JVI.00429-11. Epub 2011 Aug 31.
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.
摘要
拉沙病毒（LASV；沙粒病毒科）可引起非洲的严重出血热。LASV 核蛋白（NP）在调节病毒转录和复制以及抑制 I 型干扰素（IFN）产生方面发挥重要作用。NP 的 C 末端结构域含有参与抑制 IFN 诱导的 3'-5'外切核酸酶活性。我们已经建立了用于 LASV 的鼠聚合酶（Pol）I 反向遗传学系统，表明 NP 的残基 D389 和 G392 对于 LASV 的生存能力至关重要，而 D389A/G392A 和 D389T/392A 双突变体在抑制巨噬细胞和树突状细胞中 IFN 的能力方面发生了严重改变。评估它们在体内的减毒情况可能会在疫苗学方面开辟新的视角。
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