New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells.
New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells.
复制标题
DOI：
10.1371/journal.pone.0011159
复制
发表时间：
2010-06-17
期刊：
影响因子：
3.7
通讯作者：
Hjelle B
中科院分区：
文献类型：
--
作者：
Prescott J;Hall P;Acuna-Retamar M;Ye C;Wathelet MG;Ebihara H;Feldmann H;Hjelle B
新世界本土的汉坦病毒是汉坦病毒心肺综合征（HCPS）的病原体。这些病毒在人内皮细胞中诱导强烈的干扰素刺激基因（ISG）反应。源自非洲绿猴的 Vero E6 细胞用于繁殖汉坦病毒以及许多其他病毒。 Vero E6 细胞系用于病毒生产的效用被认为是由于它们缺乏编码 I 型干扰素 (IFN) 的基因，导致它们无法对病毒感染产生有效的先天免疫反应。干扰素 λ 是一种最近被鉴定的 III 型干扰素，其转录控制与 I 型干扰素非常相似，并以类似的方式激活先天免疫系统。我们发现 Vero E6 细胞通过分泌大量的 IFNλ 来响应汉坦病毒感染。三种新世界汉坦病毒同样能够在该细胞系中诱导 IFNλ 表达。用 Vero E6 细胞产生的病毒制剂中包含的 IFNλ，当用于感染多种非内皮细胞系时，会独立激活 ISG，而内皮细胞的先天免疫反应则专门由病毒感染引起。我们进一步表明，Sin Nombre 病毒在人肝癌细胞 (Huh7) 中复制到高滴度，而不诱导 ISG。在此，我们报告 Vero E6 细胞以高度活跃的抗病毒反应来应对病毒感染，包括分泌丰富的 IFNλ。这种细胞因子具有生物活性，当包含在病毒制剂中并呈递给人类上皮样细胞系时，会导致先天免疫反应的强烈激活。我们还表明，Huh7 和 A549 细胞系都不对汉坦病毒感染做出反应，证实这些细胞拥有的细胞质 RNA 解旋酶途径不参与汉坦病毒识别。我们证明 Vero E6 对病毒感染做出积极反应，抑制这些细胞中 IFNλ 的产生可能会增加它们对病毒传播的效用。
Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS). These viruses induce a strong interferon-stimulated gene (ISG) response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN), rendering them unable to mount an efficient innate immune response to virus infection. Interferon λ, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner. We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNλ. Three New World hantaviruses were similarly able to induce IFNλ expression in this cell line. The IFNλ contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7) without inducing ISGs. Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNλ. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNλ production in these cells might increase their utility for virus propagation.
登录
查看更多内容
影响因子：
3.6
作者：
Chew, Tracy;Noyce, Ryan;Mossman, Karen L.
通讯作者：
Mossman, Karen L.
DOI：
10.1073/pnas.192298899
发表时间：
2002-10-15
影响因子：
11.1
作者：
Geimonen, E;Neff, S;Mackow, ER
通讯作者：
Mackow, ER
DOI：
10.1073/pnas.031575198
发表时间：
2001-02-27
影响因子：
11.1
作者：
Basler, CF;Reid, AH;Taubenberger, JK
通讯作者：
Taubenberger, JK
影响因子：
5.4
作者：
Alff, Peter J.;Gavrilovskaya, Irina N.;Mackow, Erich R.
通讯作者：
Mackow, Erich R.
影响因子：
6
作者：
Ank, Nina;Paludan, Soren R.
通讯作者：
Paludan, Soren R.