Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression.
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.
Deng
Hongyu
H
Department of Molecular and Medical Pharmacology, University of California at Los Angeles, 90095-1735, USA.
Chu
Julia T
JT
Rettig
Matthew B
MB
Martinez-Maza
Otoniel
O
Sun
Ren
R
D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000378:metabolism / Q000821:virology; D015534:Trans-Activators / Q000235:genetics*; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics*
D017874:Immediate-Early Proteins; D015850:Interleukin-6; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins