人类疱疹病毒8型/卡波西肉瘤相关疱疹病毒的Rta上调人类白细胞介素-6基因表达。

Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression.

作者信息

Deng Hongyu, Chu Julia T, Rettig Matthew B, Martinez-Maza Otoniel, Sun Ren

机构信息

Department of Molecular and Medical Pharmacology, University of California at Los Angeles, 90095-1735, USA.

出版信息

Blood. 2002 Sep 1;100(5):1919-21. doi: 10.1182/blood-2002-01-0015.

DOI:10.1182/blood-2002-01-0015

PMID:12176919

Abstract

Human herpesvirus 8 (HHV-8)/Kaposi sarcoma-associated herpesvirus (KSHV) is linked to a number of malignancies thought to be driven by cytokines, including interleukin-6 (IL-6). Rta, a transcriptional activator encoded by HHV-8/KSHV, activates the viral lytic cycle leading to the expression of several viral genes implicated in viral pathogenesis. However, the effect of HHV-8/KSHV Rta on cellular genes has not been reported. We present evidence that the human IL-6 (hIL-6) gene is up-regulated by Rta. Rta potently activated (up to 164-fold) the hIL-6 promoter in a dose-dependent manner in a transient transfection reporter system. Rta also induced expression of the endogenous hIL-6 gene, as shown by enzyme-linked immunosorbent assays. Activation of the hIL-6 gene by HHV-8/KSHV supports the role of hIL-6 in the development of these malignancies.

摘要

人类疱疹病毒8型（HHV-8）/卡波西肉瘤相关疱疹病毒（KSHV）与多种被认为由细胞因子驱动的恶性肿瘤有关，包括白细胞介素-6（IL-6）。Rta是由HHV-8/KSHV编码的一种转录激活因子，它激活病毒裂解周期，导致一些与病毒发病机制有关的病毒基因表达。然而，HHV-8/KSHV Rta对细胞基因的影响尚未见报道。我们提供的证据表明，人类IL-6（hIL-6）基因被Rta上调。在瞬时转染报告系统中，Rta以剂量依赖的方式强力激活（高达164倍）hIL-6启动子。酶联免疫吸附试验表明，Rta还诱导内源性hIL-6基因的表达。HHV-8/KSHV对hIL-6基因的激活支持了hIL-6在这些恶性肿瘤发生发展中的作用。