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Lassa virus nucleoprotein mutants generated by reverse genetics induce a robust type I interferon response in human dendritic cells and macrophages.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。
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2
The exonuclease domain of Lassa virus nucleoprotein is involved in antigen-presenting-cell-mediated NK cell responses.拉沙病毒核蛋白的核酸外切酶结构域参与抗原呈递细胞介导的自然杀伤细胞反应。
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3
Lassa virus activates myeloid dendritic cells but suppresses their ability to stimulate T cells.拉沙病毒激活髓样树突状细胞，但抑制其刺激 T 细胞的能力。
PLoS Pathog. 2018 Nov 12;14(11):e1007430. doi: 10.1371/journal.ppat.1007430. eCollection 2018 Nov.
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Alphavirus vector-based replicon particles expressing multivalent cross-protective Lassa virus glycoproteins.基于阿尔巴病毒载体的复制子颗粒表达具有多价交叉保护作用的拉沙病毒糖蛋白。
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Non-Pathogenic Mopeia Virus Induces More Robust Activation of Plasmacytoid Dendritic Cells than Lassa Virus.非致病 Mopeia 病毒比拉沙病毒诱导更强烈的浆细胞样树突状细胞激活。
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Recombinant Lassa Virus Expressing Green Fluorescent Protein as a Tool for High-Throughput Drug Screens and Neutralizing Antibody Assays.表达绿色荧光蛋白的重组拉沙病毒作为高通量药物筛选和中和抗体检测的工具。
Viruses. 2018 Nov 20;10(11):655. doi: 10.3390/v10110655.
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Role of interferons in the control of Lassa virus replication in human dendritic cells and macrophages.干扰素在控制拉沙病毒在人树突状细胞和巨噬细胞中复制的作用。
Microbes Infect. 2006 Apr;8(5):1194-202. doi: 10.1016/j.micinf.2006.02.002. Epub 2006 Mar 20.
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Production of CXC and CC chemokines by human antigen-presenting cells in response to Lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever.人类抗原呈递细胞对拉沙病毒或密切相关的免疫原性病毒以及感染拉沙热的食蟹猴的反应中CXC和CC趋化因子的产生
PLoS Negl Trop Dis. 2014 Jan 9;8(1):e2637. doi: 10.1371/journal.pntd.0002637. eCollection 2014.
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Infection of Human Endothelial Cells with Lassa Virus Induces Early but Transient Activation and Low Type I IFN Response Compared to the Closely-Related Nonpathogenic Mopeia Virus.与密切相关的非致病性 Mopeia 病毒相比，拉沙病毒感染人血管内皮细胞会引起早期但短暂的激活和低水平的 I 型干扰素反应。
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本文引用的文献

1
Human dendritic cells infected with the nonpathogenic Mopeia virus induce stronger T-cell responses than those infected with Lassa virus.人类树突状细胞感染非致病性 Mopeia 病毒比感染拉沙病毒诱导更强的 T 细胞反应。
J Virol. 2011 Aug;85(16):8293-306. doi: 10.1128/JVI.02120-10. Epub 2011 Jun 1.
2
Efficient rescue of recombinant Lassa virus reveals the influence of S segment noncoding regions on virus replication and virulence.高效拯救重组拉沙病毒揭示 S 片段非编码区对病毒复制和毒力的影响。
J Virol. 2011 Apr;85(8):4020-4. doi: 10.1128/JVI.02556-10. Epub 2011 Feb 9.
3
Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression.拉沙病毒核蛋白结构揭示了一种 dsRNA 特异性 3' 到 5' 外切酶活性，对于免疫抑制至关重要。
Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2396-401. doi: 10.1073/pnas.1016404108. Epub 2011 Jan 24.
4
Use of single-cycle infectious lymphocytic choriomeningitis virus to study hemorrhagic fever arenaviruses.利用单循环传染性淋巴细胞脉络丛脑膜炎病毒研究出血热沙粒病毒。
J Virol. 2011 Feb;85(4):1684-95. doi: 10.1128/JVI.02229-10. Epub 2010 Dec 1.
5
Cap binding and immune evasion revealed by Lassa nucleoprotein structure.拉沙病毒核蛋白结构揭示的帽子结合和免疫逃逸。
Nature. 2010 Dec 9;468(7325):779-83. doi: 10.1038/nature09605. Epub 2010 Nov 17.
6
Reverse genetics generation of chimeric infectious Junin/Lassa virus is dependent on interaction of homologous glycoprotein stable signal peptide and G2 cytoplasmic domains.反向遗传学生成嵌合传染性胡宁/拉萨病毒依赖于同源糖蛋白稳定信号肽和 G2 胞质结构域的相互作用。
J Virol. 2011 Jan;85(1):112-22. doi: 10.1128/JVI.01837-10. Epub 2010 Oct 27.
7
Identification of amino acid residues critical for the anti-interferon activity of the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus.鉴定原型沙粒病毒淋巴细胞性脉络丛脑膜炎病毒核蛋白抗干扰素活性的关键氨基酸残基。
J Virol. 2009 Nov;83(21):11330-40. doi: 10.1128/JVI.00763-09. Epub 2009 Aug 26.
8
Development of infectious clones for virulent and avirulent pichinde viruses: a model virus to study arenavirus-induced hemorrhagic fevers.强毒和无毒皮钦德病毒感染性克隆的构建：一种用于研究沙粒病毒引起的出血热的模型病毒
J Virol. 2009 Jul;83(13):6357-62. doi: 10.1128/JVI.00019-09. Epub 2009 Apr 22.
9
Efficient reverse genetics generation of infectious junin viruses differing in glycoprotein processing.高效反向遗传学产生糖蛋白加工方式不同的感染性胡宁病毒
J Virol. 2009 Jun;83(11):5606-14. doi: 10.1128/JVI.00276-09. Epub 2009 Mar 25.
10
Early and strong immune responses are associated with control of viral replication and recovery in lassa virus-infected cynomolgus monkeys.早期且强烈的免疫反应与拉沙病毒感染的食蟹猴体内病毒复制的控制及恢复相关。
J Virol. 2009 Jun;83(11):5890-903. doi: 10.1128/JVI.01948-08. Epub 2009 Mar 18.

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.

DOI:10.1128/JVI.00429-11
PMID:21880754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3209271/
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。