2′-5′ Oligoadenylate Synthetase Plays a Critical Role in Interferon-γ Inhibition of Respiratory Syncytial Virus Infection of Human Epithelial Cells*
2′-5′ Oligoadenylate Synthetase Plays a Critical Role in Interferon-γ Inhibition of Respiratory Syncytial Virus Infection of Human Epithelial Cells*
复制标题
2′-5′寡腺苷酸合成酶在干扰素-γ 抑制人上皮细胞呼吸道合胞病毒感染中发挥关键作用*
DOI：
--
复制
发表时间：
2002
影响因子：
4.8
通讯作者：
S. Mohapatra
中科院分区：
文献类型：
--
作者：
A. Behera;Mukesh Kumar;R. Lockey;S. Mohapatra
呼吸道合胞病毒与毛细支气管炎和哮喘有关，对I型干扰素的抗病毒作用有抵抗力，但对干扰素-γ没有抵抗力。然而，干扰素-γ抗呼吸道合胞病毒感染的抗病毒机制尚不清楚。本研究以人上皮细胞系HEP-2和A549为研究对象，探讨了干扰素-γ诱导抗病毒作用的分子机制。在呼吸道合胞病毒感染之前或之后，将这些细胞暴露在100-1000个单位/毫升的干扰素-γ中，可以显著降低呼吸道合胞病毒的感染率。作用1h后，干扰素-γ可诱导细胞内干扰素调节因子-1的蛋白表达，但不能诱导双链核糖核酸激活的蛋白激酶和诱导型一氧化氮合酶的表达。在干扰素-γ作用1h和4h时，2‘-5’寡腺苷合成酶(2-5AS)的IRF-1、p40和p69亚型均可检测到。使用放线菌酮和反义寡核苷酸对IRF-1的研究表明，IRF-1在激活2-5 AS中具有直接作用。转染反义寡核苷酸2-5的细胞可抑制干扰素-γ的抗病毒作用。与HEP-2细胞相比，稳定表达核糖核酸酶L抑制剂的HEP-2细胞株RNase L活性和干扰素-γ介导的抗病毒作用显著降低，其基因表达模式与亲本细胞相似。这些结果为2-5AS参与干扰素-γ−介导的抗病毒活性提供了直接证据。
Respiratory syncytial virus (RSV), associated with bronchiolitis and asthma, is resistant to the antiviral effects of type-I interferons (IFN), but not IFN-γ. However, the antiviral mechanism of IFN-γ action against RSV infection is unknown. The molecular mechanism of IFN-γ-induced antiviral activity was examined in this study using human epithelial cell lines HEp-2 and A549. Exposure of these cells to 100–1000 units/ml of IFN-γ, either before or after RSV infection, results in a significant decrease in RSV infection. After 1 h of exposure, IFN-γ induces protein expression of IFN regulatory factor-1 (IRF-1) but not IRF-2, double-stranded RNA-activated protein kinase, and inducible nitric-oxide synthase in these cells. The mRNA for IRF-1, p40, and p69 isoforms of 2′-5′ oligoadenylate synthetase (2–5 AS) are detectable, respectively, at 1 and 4 h of IFN-γ exposure. Studies using cycloheximide and antisense oligonucleotides to IRF-1 indicate a direct role of IRF-1 in activating 2–5 AS. Cells transfected with 2–5 AS antisense oligonucleotides inhibit the antiviral effect of IFN-γ. A stable cell line of HEp-2 overexpressing RNase L inhibitor, RLI-14, which exhibits an IFN-γ-induced gene expression pattern similar to that of the parent cell line, shows a significant reduction in RNase L activity and IFN-γ-mediated antiviral effect, compared with HEp-2 cells. These results provide direct evidence of the involvement of 2–5 AS in IFN-γ−mediated antiviral activity in these cells.
登录
查看更多内容
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
人干扰素调节因子2基因。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Cha,Y;Deisseroth,AB
通讯作者：
Deisseroth,AB
影响因子：
56.9
作者：
KIMURA, T;NAKAYAMA, K;TANIGUCHI, T
通讯作者：
TANIGUCHI, T
影响因子：
11.8
作者：
Hall, CB
通讯作者：
Hall, CB
影响因子：
56.9
作者：
FLOYDSMITH, G;SLATTERY, E;LENGYEL, P
通讯作者：
LENGYEL, P