hTERT extends the life of human fibroblasts without compromising type I interferon signaling.
hTERT extends the life of human fibroblasts without compromising type I interferon signaling.
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DOI：
10.1371/journal.pone.0058233
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Davido DJ
中科院分区：
文献类型：
--
作者：
Smith MC;Goddard ET;Perusina Lanfranca M;Davido DJ
原代细胞通常用于研究病毒复制和宿主-病毒相互作用，因为它们的抗病毒途径尚未改变或失活；然而，它们的使用因其寿命短而受到限制。延长原代培养物寿命的传统方法通常利用病毒癌基因。然而，许多致癌基因会扰乱或灭活细胞抗病毒途径，包括干扰素 (IFN) 反应。先前的研究表明，端粒酶逆转录酶（TERT）基因的表达可以延长某些细胞类型的寿命。 TERT 表达对含 RNA 和 DNA 病毒的先天抗病毒反应的影响尚未得到研究。在当前的研究中，我们将人类 TERT (hTERT) 基因引入原代人类胚胎肺 (HEL-299) 细胞株中，该细胞株已知对 I 型干扰素（IFN-β）有反应。我们证明，由此产生的 HEL-TERT 细胞系能够复制超过 100 次群体倍增，而不会表现出衰老迹象。 IFN-β 治疗导致 HEL-299 和 HEL-TERT 细胞中四个模型 IFN 刺激基因 (ISG) 上调。两种细胞系均支持 1 型单纯疱疹病毒 (HSV-1) 和水疱性口炎病毒 (VSV) 的复制，并在 IFN-β 预处理后损害这两种病毒的复制。病毒癌蛋白、猿猴病毒 40 (SV40) 大 T 抗原（常用于使细胞永生化）的引入在很大程度上消除了这种效应。综上所述，我们的数据表明 hTERT 的表达不会改变 1 型 IFN 信号传导和/或两种病毒的生长，使该细胞系成为研究病毒复制和病毒与细胞相互作用的有用试剂。
Primary cells are often used to study viral replication and host-virus interactions as their antiviral pathways have not been altered or inactivated; however, their use is restricted by their short lifespan. Conventional methods to extend the life of primary cultures typically utilize viral oncogenes. Many of these oncogenes, however, perturb or inactivate cellular antiviral pathways, including the interferon (IFN) response. It has been previously shown that expression of the telomerase reverse transcriptase (TERT) gene extends the life of certain cell types. The effect that TERT expression has on the innate antiviral response to RNA- and DNA-containing viruses has not been examined. In the current study, we introduced the human TERT (hTERT) gene into a primary human embryonic lung (HEL-299) cell strain, which is known to respond to the type I IFN, IFN-β. We show that the resulting HEL-TERT cell line is capable of replicating beyond 100 population doublings without exhibiting signs of senescence. Treatment with IFN-β resulted in the upregulation of four model IFN stimulated genes (ISGs) in HEL-299 and HEL-TERT cells. Both cell lines supported the replication of herpes simplex virus type 1 (HSV-1) and vesicular stomatitis virus (VSV) and impaired the replication of both viruses upon IFN-β pretreatment. Introduction of the viral oncoprotein, simian virus 40 (SV40) large T-antigen, which is frequently used to immortalize cells, largely negated this effect. Taken together, our data indicate that expression of hTERT does not alter type 1 IFN signaling and/or the growth of two viruses, making this cell line a useful reagent for studying viral replication and virus-cell interactions.
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影响因子：
5.4
作者：
Conrady, Christopher D.;Halford, William P.;Carr, Daniel J. J.
通讯作者：
Carr, Daniel J. J.
影响因子：
14.9
作者：
Dimmer EC;Huntley RP;Alam-Faruque Y;Sawford T;O'Donovan C;Martin MJ;Bely B;Browne P;Mun Chan W;Eberhardt R;Gardner M;Laiho K;Legge D;Magrane M;Pichler K;Poggioli D;Sehra H;Auchincloss A;Axelsen K;Blatter MC;Boutet E;Braconi-Quintaje S;Breuza L;Bridge A;Coudert E;Estreicher A;Famiglietti L;Ferro-Rojas S;Feuermann M;Gos A;Gruaz-Gumowski N;Hinz U;Hulo C;James J;Jimenez S;Jungo F;Keller G;Lemercier P;Lieberherr D;Masson P;Moinat M;Pedruzzi I;Poux S;Rivoire C;Roechert B;Schneider M;Stutz A;Sundaram S;Tognolli M;Bougueleret L;Argoud-Puy G;Cusin I;Duek-Roggli P;Xenarios I;Apweiler R
通讯作者：
Apweiler R
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
5.4
作者：
Davido, DJ;von Zagorski, WF;Schaffer, PA
通讯作者：
Schaffer, PA
影响因子：
10.5
作者：
DEBBAS, M;WHITE, E
通讯作者：
WHITE, E