CD95 Signaling Inhibits B Cell Receptor-Mediated Gammaherpesvirus Replication in Apoptosis-Resistant B Lymphoma Cells
CD95 Signaling Inhibits B Cell Receptor-Mediated Gammaherpesvirus Replication in Apoptosis-Resistant B Lymphoma Cells
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CD95 信号传导抑制抗凋亡 B 淋巴瘤细胞中 B 细胞受体介导的 γ-疱疹病毒复制
DOI：
10.1128/jvi.00668-16
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发表时间：
2016-08
影响因子：
5.4
通讯作者：
Liang Xiaozhen
中科院分区：
文献类型：
--
作者：
Tan Lingbing;Zhang Chaocan;Dematos Julien;Kuang Linlin;Jung Jae U.;Liang Xiaozhen
CD 95是一种凋亡诱导受体，已成为一种潜在的抗癌治疗靶点，越来越多的证据表明，CD 95也通过激活非凋亡信号通路而成为一种肿瘤促进剂。γ疱疹病毒感染与淋巴增生性疾病密切相关，包括B细胞淋巴瘤。CD 95在γ疱疹病毒相关淋巴瘤中的非凋亡功能在很大程度上是未知的。在这里，我们表明，刺激的CD 95激动剂抗体驱动大多数敏感的γ疱疹病毒转化的B细胞进行半胱天冬酶依赖性凋亡，并促进抗凋亡B细胞亚群的生存和增殖。令人惊讶的是，CD 95介导的非凋亡信号诱导β干扰素（IFN-β）表达，并相关地抑制B细胞受体（BCR）介导的γ疱疹病毒复制，而不影响BCR信号。进一步分析表明IFN-β单独或与CD 95协同作用可阻断γ疱疹病毒裂解开关蛋白的激活和基因表达。我们的研究结果表明，独立于其凋亡活性，CD 95信号传导活性在阻断抗肿瘤，γ疱疹病毒相关的B淋巴瘤细胞中的病毒复制中起着重要作用，这表明宿主CD 95原型死亡受体如何独立于其凋亡活性控制γ疱疹病毒的生命周期的新机制。重要性γ疱疹病毒与淋巴系统恶性肿瘤和其他癌症密切相关。导致癌症的病毒复制和持续策略涉及抗凋亡和增殖程序的激活，以及逃避宿主免疫应答。在这里，我们提供的证据表明，刺激的CD 95激动剂抗体，模拟细胞毒性T细胞杀伤的主要机制之一，抑制B细胞受体介导的γ疱疹病毒复制的CD 95免疫耐受性淋巴瘤细胞。CD 95诱导的I型干扰素（IFN-β）有助于抑制γ疱疹病毒复制。这一发现为CD 95的非凋亡功能提供了新的线索，并为γ疱疹病毒提供了一种新的机制，帮助它们逃避宿主的免疫监视。
ABSTRACT While CD95 is an apoptosis-inducing receptor and has emerged as a potential anticancer therapy target, mounting evidence shows that CD95 is also emerging as a tumor promoter by activating nonapoptotic signaling pathways. Gammaherpesviral infection is closely associated with lymphoproliferative diseases, including B cell lymphomas. The nonapoptotic function of CD95 in gammaherpesvirus-associated lymphomas is largely unknown. Here, we show that stimulation of CD95 agonist antibody drives the majority of sensitive gammaherpesvirus-transformed B cells to undergo caspase-dependent apoptosis and promotes the survival and proliferation of a subpopulation of apoptosis-resistant B cells. Surprisingly, CD95-mediated nonapoptotic signaling induced beta interferon (IFN-β) expression and correlatively inhibited B cell receptor (BCR)-mediated gammaherpesviral replication in the apoptosis-resistant lymphoma cells without influencing BCR signaling. Further analysis showed that IFN-β alone or synergizing with CD95 blocked the activation of lytic switch proteins and the gene expression of gammaherpesviruses. Our findings indicate that, independent of its apoptotic activity, CD95 signaling activity plays an important role in blocking viral replication in apoptosis-resistant, gammaherpesvirus-associated B lymphoma cells, suggesting a novel mechanism that indicates how host CD95 prototype death receptor controls the life cycle of gammaherpesviruses independent of its apoptotic activity. IMPORTANCE Gammaherpesviruses are closely associated with lymphoid malignancies and other cancers. Viral replication and persistence strategies leading to cancer involve the activation of antiapoptotic and proliferation programs, as well as evasion of the host immune response. Here, we provide evidence that the stimulation of CD95 agonist antibody, mimicking one of the major mechanisms of cytotoxic T cell killing, inhibits B cell receptor-mediated gammaherpesviral replication in CD95 apoptosis-resistant lymphoma cells. CD95-induced type I interferon (IFN-β) contributes to the inhibition of gammaherpesviral replication. This finding sheds new light on the CD95 nonapoptotic function and provides a novel mechanism for gammaherpesviruses that helps them to escape host immune surveillance.
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影响因子：
1.6
作者：
T. Satoh;Y. Hoshikawa;Yukio Satoh;T. Kurata;T. Sairenji
通讯作者：
T. Satoh;Y. Hoshikawa;Yukio Satoh;T. Kurata;T. Sairenji
影响因子：
16.6
作者：
Ceppi, Paolo;Hadji, Abbas;Kohlhapp, Frederick J.;Pattanayak, Abhinandan;Hau, Annika;Liu, Xia;Liu, Huiping;Murmann, Andrea E.;Peter, Marcus E.
通讯作者：
Peter, Marcus E.
影响因子：
64.5
作者：
THANOS, D;MANIATIS, T
通讯作者：
MANIATIS, T
影响因子：
20.3
作者：
Le Clorennec, C;Youlyouz-Marfak, I;Feuillard, J
通讯作者：
Feuillard, J
DOI：
10.1016/s0140-6736(18)31578-2
发表时间：
1890-04
期刊：
The Hospital
影响因子：
--
作者：
Samir Guglani
通讯作者：
Samir Guglani