Herpes simplex virus type 2 triggers reactivation of Kaposi's sarcoma-associated herpesvirus from latency and collaborates with HIV-1 Tat.
Herpes simplex virus type 2 triggers reactivation of Kaposi's sarcoma-associated herpesvirus from latency and collaborates with HIV-1 Tat.
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DOI：
10.1371/journal.pone.0031652
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lu C
中科院分区：
文献类型：
--
作者：
Tang Q;Qin D;Lv Z;Zhu X;Ma X;Yan Q;Zeng Y;Guo Y;Feng N;Lu C
卡波西肉瘤相关疱疹病毒（KSHV）感染是必要的，但不足以卡波西肉瘤（KS）的发展没有其他辅因子。以前，我们发现，人类免疫缺陷病毒1型（HIV-1）达特和单纯疱疹病毒1型（HSV-1）是重要的辅因子，重新激活KSHV从潜伏期。在这里，我们进一步研究了单纯疱疹病毒2型（HSV-2）影响KSHV复制的潜力，并研究了达特在这一过程中的作用。我们证明，HSV-2是一个潜在的重要因素，在KS的发病机制，确定在BCBL-1细胞的裂解期mRNA转录，病毒蛋白和感染性病毒颗粒的生产。这些结果通过使用靶向KSHV Rta的小干扰RNA的RNA干扰实验和测试Rta启动子驱动的荧光素酶活性的荧光素酶报告基因测定进一步证实。机制研究表明HSV-2感染激活了核因子-κ B（NF-κB）信号通路。抑制NF-κB通路可增强HSV-2介导的KSHV激活，而激活NF-κB通路可抑制HSV-2感染的BCBL-1细胞中KSHV的复制。此外，异位表达的达特增强HSV-2诱导的KSHV复制。这些新的发现提示HSV-2在KS发病机制中的作用，并首次提供实验室证据证明达特可能参与HSV-2介导的KSHV激活，暗示获得性免疫缺陷综合征（AIDS）相关KS（AIDS-KS）患者的发病机制复杂。
Kaposi's sarcoma-associated herpesvirus (KSHV) infection was necessary but not sufficient for Kaposi's sarcoma (KS) development without other cofactors. Previously, we identified that both human immunodeficiency type 1 (HIV-1) Tat and herpes simplex virus 1 (HSV-1) were important cofactors reactivating KSHV from latency. Here, we further investigated the potential of herpes simplex virus 2 (HSV-2) to influence KSHV replication and examined the role of Tat in this procedure. We demonstrated that HSV-2 was a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV Rta and a luciferase reporter assay testing Rta promoter-driven luciferase activity. Mechanistic studies showed that HSV-2 infection activated nuclear factor-kappa B (NF-κB) signaling pathway. Inhibition of NF-κB pathway enhanced HSV-2-mediated KSHV activation, whereas activation of NF-κB pathway suppressed KSHV replication in HSV-2-infected BCBL-1 cells. Additionally, ectopic expression of Tat enhanced HSV-2-induced KSHV replication. These novel findings suggest a role of HSV-2 in the pathogenesis of KS and provide the first laboratory evidence that Tat may participate HSV-2-mediated KSHV activation, implying the complicated pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS (AIDS-KS) patients.
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影响因子：
5.4
作者：
Izumiya, Yoshihiro;Izumiya, Chie;Kung, Hsing-Jien
通讯作者：
Kung, Hsing-Jien
影响因子：
4.6
作者：
Kim, YC;Bang, D;Lee, KH
通讯作者：
Lee, KH
影响因子：
4.6
作者：
Bergstrom, T;Trybala, E
通讯作者：
Trybala, E
影响因子：
3.8
作者：
Malope, Babatyi I.;MacPhail, Patrick;Whitby, Denise
通讯作者：
Whitby, Denise
影响因子：
5.4
作者：
Hancock, Meaghan H.;Cliffe, Anna R.;Smiley, James R.
通讯作者：
Smiley, James R.