RIG-I enhanced interferon independent apoptosis upon Junin virus infection.
RIG-I enhanced interferon independent apoptosis upon Junin virus infection.
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DOI：
10.1371/journal.pone.0099610
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Paessler S
中科院分区：
文献类型：
--
作者：
Kolokoltsova OA;Grant AM;Huang C;Smith JK;Poussard AL;Tian B;Brasier AR;Peters CJ;Tseng CT;de la Torre JC;Paessler S
Junin病毒（JUNV）是阿根廷出血热（AHF）的病原，是一种高致死率的人类疾病。人们普遍认为，包括JUNV感染在内的沙粒病毒感染通常是非细胞病变的。相比之下，本研究通过磷脂酰丝氨酸（PS）易位、Caspase 3 （CASP3）激活、聚（adp -核糖）聚合酶（PARP）裂解和/或染色体DNA断裂检测，证实JUNV减毒Candid#1菌株感染人肺上皮癌（A549）、人肝癌和Vero细胞诱导凋亡。此外，通过DNA片段分析，我们发现JUNV致病性Romero菌株在人肝癌和Vero中的细胞病变程度低于Candid#1，但在A549和Vero E6细胞中凋亡程度更高。此外，我们发现junv诱导的细胞凋亡可通过RIG-I信号通路增强。与之前报道的RIG-I样解旋酶（RLH）信号在启动程序性细胞死亡中的作用一致，我们发现，尽管病毒产量增加，但在siRNA或shRNA沉默RIG-I通路组分后，Candid#1感染的A549细胞的细胞死亡或DNA断裂减少。同样，我们观察到junv感染的缺乏RIG-I的人肝癌细胞的DNA片段化程度比RIG-I正常的细胞要低。此外，在I型干扰素（IFN）缺陷的Vero细胞Candid#1感染时检测到的DNA片段表明，JUNV诱导的I型干扰素（IFN）不依赖于IFN的凋亡机制。我们的工作首次证明了多种哺乳动物源性细胞对JUNV感染的细胞凋亡诱导及其细胞死亡的部分机制。
Junin virus (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF), a human disease with a high case-fatality rate. It is widely accepted that arenaviral infections, including JUNV infections, are generally non-cytopathic. In contrast, here we demonstrated apoptosis induction in human lung epithelial carcinoma (A549), human hepatocarcinoma and Vero cells upon infection with the attenuated Candid#1 strain of, JUNV as determined by phosphatidylserine (PS) translocation, Caspase 3 (CASP3) activation, Poly (ADP-ribose) polymerase (PARP) cleavage and/or chromosomal DNA fragmentation. Moreover, as determined by DNA fragmentation, we found that the pathogenic Romero strain of JUNV was less cytopathic than Candid#1 in human hepatocarcinoma and Vero, but more apoptotic in A549 and Vero E6 cells. Additionally, we found that JUNV-induced apoptosis was enhanced by RIG-I signaling. Consistent with the previously reported role of RIG-I like helicase (RLH) signaling in initiating programmed cell death, we showed that cell death or DNA fragmentation of Candid#1-infected A549 cells was decreased upon siRNA or shRNA silencing of components of RIG-I pathway in spite of increased virus production. Similarly, we observed decreased DNA fragmentation in JUNV-infected human hepatocarcinoma cells deficient for RIG-I when compared with that of RIG-I-competent cells. In addition, DNA fragmentation detected upon Candid#1 infection of type I interferon (IFN)-deficient Vero cells suggested a type I IFN-independent mechanism of apoptosis induction in response to JUNV. Our work demonstrated for the first time apoptosis induction in various cells of mammalian origin in response to JUNV infection and partial mechanism of this cell death.
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影响因子：
6.4
作者：
CARBALLAL, G;COSSIO, PM;ARANA, RM
通讯作者：
ARANA, RM
影响因子：
3.7
作者：
García, JB;Morzunov, SP;St Jeort, SC
通讯作者：
St Jeort, SC
影响因子：
3.8
作者：
Albarino, CG;Ghiringhelli, PD;Romanowski, V
通讯作者：
Romanowski, V
影响因子：
1.6
作者：
Goñi, SE;Iserte, JA;Lozano, ME
通讯作者：
Lozano, ME
DOI：
10.1099/vir.0.052910-0
发表时间：
2013-08
期刊：
The Journal of general virology
影响因子：
--
作者：
de Wilde AH;Raj VS;Oudshoorn D;Bestebroer TM;van Nieuwkoop S;Limpens RWAL;Posthuma CC;van der Meer Y;Bárcena M;Haagmans BL;Snijder EJ;van den Hoogen BG
通讯作者：
van den Hoogen BG