The interferon-stimulated gene product oligoadenylate synthetase-like protein enhances replication of Kaposi's sarcoma-associated herpesvirus (KSHV) and interacts with the KSHV ORF20 protein.
The interferon-stimulated gene product oligoadenylate synthetase-like protein enhances replication of Kaposi's sarcoma-associated herpesvirus (KSHV) and interacts with the KSHV ORF20 protein.
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DOI：
10.1371/journal.ppat.1006937
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发表时间：
2018-03
期刊：
影响因子：
6.7
通讯作者：
Brinkmann MM
中科院分区：
文献类型：
--
作者：
Bussey KA;Lau U;Schumann S;Gallo A;Osbelt L;Stempel M;Arnold C;Wissing J;Gad HH;Hartmann R;Brune W;Jänsch L;Whitehouse A;Brinkmann MM
卡波西肉瘤相关疱疹病毒（KSHV）是迄今为止已知的少数致癌人类病毒之一。其庞大的基因组编码超过 85 种蛋白质，包括独特的病毒蛋白质以及疱疹病毒中保守的蛋白质。 KSHV ORF20是疱疹病毒核心UL24家族的成员，但ORF20的功能及其在病毒生命周期中的作用尚不清楚。 ORF20 编码三种很大程度上未表征的亚型，我们发现它们主要位于细胞核和核仁中。定量亲和纯化与质谱联用 (q-AP-MS) 鉴定了 ORF20 的许多特定相互作用伙伴，包括核糖体蛋白和干扰素刺激基因产物 (ISG) 寡腺苷酸合成酶样蛋白 (OASL)。内源性和瞬时转染的 OASL 均与 ORF20 共免疫沉淀，并且这种相互作用在其他疱疹病毒中 UL24 家族的所有 ORF20 同工型和多个 ORF20 同源物中都是保守的。通过 q-AP-MS 对 OASL 相互作用伙伴的表征发现了与 ORF20 非常相似的相互作用组。 ORF20和OASL均与40S和60S核糖体亚基共纯化，当它们共表达时，它们与多核糖体结合。尽管ORF20对翻译没有整体影响，但ORF20以IRF3依赖但不依赖IFNAR的方式增强RIG-I诱导的内源性OASL表达。 OASL 已被定性为对某些病毒具有抗病毒活性的 ISG，但其对伽马疱疹病毒的作用尚不清楚。我们发现，潜伏感染的 HuARLT-rKSHV.219 细胞重新激活后早期就诱导了 OASL 和 ORF20 mRNA 表达。有趣的是，我们发现 OASL 增强了 KSHV 的感染。然而，在感染 KSHV ORF20stop 突变体期间，OASL 依赖性的感染性增强作用消失了。我们的数据描述了 ORF20 与 OASL 的相互作用，并表明 ORF20 篡夺了 OASL 的功能以利于 KSHV 感染。疱疹病毒是大型双链 DNA 病毒家族，可引起从水痘到癌症等多种疾病。卡波西肉瘤相关疱疹病毒 (KSHV) 是一种致癌疱疹病毒，可导致卡波西肉瘤的发展，卡波西肉瘤是 HIV 阳性患者的一种主要癌症形式。与所有疱疹病毒一样，KSHV 感染是终生的。 KSHV 究竟如何启动和维持其感染尚不清楚，但它必须操纵宿主细胞以建立有利的条件。同样，宿主也发展出了一套复杂的系统来抵御入侵者，其中包括产生干扰素刺激的基因产物。我们现在发现 KSHV 利用了一种这样的宿主细胞蛋白，即寡腺苷酸合成酶样蛋白 (OASL)。 OASL 不像在许多其他病毒感染期间那样充当抗病毒蛋白，KSHV 似乎已经找到了一种利用 OASL 来实现自身利益的方法。 KSHV 蛋白 ORF20 与 OASL 相互作用，它们共定位于核仁中，并且 ORF20 和 OASL 都与细胞翻译机制的组件相关联并纯化。这可能通过选择性控制蛋白质的产生来帮助病毒感染。
Kaposi’s sarcoma-associated herpesvirus (KSHV) is one of the few oncogenic human viruses known to date. Its large genome encodes more than 85 proteins and includes both unique viral proteins as well as proteins conserved amongst herpesviruses. KSHV ORF20 is a member of the herpesviral core UL24 family, but the function of ORF20 and its role in the viral life cycle is not well understood. ORF20 encodes three largely uncharacterized isoforms, which we found were localized predominantly in the nuclei and nucleoli. Quantitative affinity purification coupled to mass spectrometry (q-AP-MS) identified numerous specific interacting partners of ORF20, including ribosomal proteins and the interferon-stimulated gene product (ISG) oligoadenylate synthetase-like protein (OASL). Both endogenous and transiently transfected OASL co-immunoprecipitated with ORF20, and this interaction was conserved among all ORF20 isoforms and multiple ORF20 homologs of the UL24 family in other herpesviruses. Characterization of OASL interacting partners by q-AP-MS identified a very similar interactome to that of ORF20. Both ORF20 and OASL copurified with 40S and 60S ribosomal subunits, and when they were co-expressed, they associated with polysomes. Although ORF20 did not have a global effect on translation, ORF20 enhanced RIG-I induced expression of endogenous OASL in an IRF3-dependent but IFNAR-independent manner. OASL has been characterized as an ISG with antiviral activity against some viruses, but its role for gammaherpesviruses was unknown. We show that OASL and ORF20 mRNA expression were induced early after reactivation of latently infected HuARLT-rKSHV.219 cells. Intriguingly, we found that OASL enhanced infection of KSHV. During infection with a KSHV ORF20stop mutant, however, OASL-dependent enhancement of infectivity was lost. Our data have characterized the interaction of ORF20 with OASL and suggest ORF20 usurps the function of OASL to benefit KSHV infection. The herpesviruses are a family of large double-stranded DNA viruses that cause a variety of illnesses from chicken pox to cancer. Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-causing herpesvirus and can lead to development of Kaposi’s sarcoma, a major form of cancer in HIV-positive patients. As for all herpesviruses, infection with KSHV is lifelong. Exactly how KSHV initiates and maintains its infection is still not well understood, but it must manipulate the host cell to establish favorable conditions. Likewise, the host has developed a complicated system to fight off invaders, which includes the production of interferon-stimulated gene products. We have now found that KSHV exploits one such host cell protein, the oligoadenylate synthetase-like protein (OASL). Rather than OASL acting as an antiviral protein as it does during many other viral infections, KSHV appears to have found a way to utilize OASL for its own benefit. The KSHV protein ORF20 interacts with OASL, they co-localize in nucleoli, and both ORF20 and OASL associate and purify with components of the cellular translational machinery. This may help viral infection by selectively controlling protein production.
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影响因子：
5.4
作者：
Boritz, E;Gerlach, J;Rose, JK
通讯作者：
Rose, JK
DOI：
10.1038/nri3719
发表时间：
2014-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Hornung V;Hartmann R;Ablasser A;Hopfner KP
通讯作者：
Hopfner KP
影响因子：
16
作者：
Davis, Zoe H.;Verschueren, Erik;Jang, Gwendolyn M.;Kleffman, Kevin;Johnson, Jeffrey R.;Park, Jimin;Von Dollen, John;Maher, M. Cyrus;Johnson, Tasha;Newton, William;Jaeger, Stefanie;Shales, Michael;Horner, Julie;Hernandez, Ryan D.;Krogan, Nevan J.;Glaunsinger, Britt A.
通讯作者：
Glaunsinger, Britt A.
2′-5′ 寡腺苷酸合成酶样蛋白 p59 OASL 与转录抑制因子甲基 CpG 结合蛋白 1 之间的相互作用
DOI：
10.1046/j.1432-1033.2003.03966.x
发表时间：
2004-02-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Andersen, JB;Strandbygård, DJ;Justesen, J
通讯作者：
Justesen, J
影响因子：
5.4
作者：
Alkharsah, Khaled R.;Singh, Vivek Vikram;Schulz, Thomas F.
通讯作者：
Schulz, Thomas F.