Roan Florence, Zimring James C, Goodbourn Stephen, Offermann Margaret K
Program in Biochemistry, Cell and Developmental Biology2 and Department of Medicine4, Emory University, Atlanta, GA 30322, USA.
Winship Cancer Center, Emory University, 1365-B Clifton Road NE, Atlanta, GA 30322, USA1.
J Gen Virol. 1999 Aug;80 ( Pt 8):2205-2209. doi: 10.1099/0022-1317-80-8-2205.
Human herpesvirus-8 (HHV-8), a gammaherpesvirus that is thought to be the viral aetiologic agent of Kaposi's sarcoma and primary effusion lymphoma, encodes a homologue to cellular interferon regulatory factors (IRFs). The HHV-8 IRF homologue (vIRF; ORF K9) has previously been shown to inhibit gene induction by interferons and IRF-1 and to transform NIH3T3 cells or Rat-1 cells. Additionally, expression of antisense to vIRF in BCBL-1 cells results in the repression of certain HHV-8 genes, suggesting that vIRF may also positively regulate gene expression. We demonstrate that vIRF activates transcription when directed to DNA by the GAL4 DNA-binding domain. GAL-vIRF truncation constructs that individually are incapable of activating transcription can cooperate in transactivation when coexpressed in HeLa cells, suggesting that multiple regions of vIRF are involved in transactivation. These studies broaden the potential mechanisms of action of vIRF to include transcriptional activation as well as transcriptional repression.
人疱疹病毒8型(HHV - 8)是一种γ疱疹病毒,被认为是卡波西肉瘤和原发性渗出性淋巴瘤的病毒病原体,它编码一种与细胞干扰素调节因子(IRFs)同源的蛋白。此前已表明,HHV - 8 IRF同源蛋白(vIRF;开放阅读框K9)可抑制干扰素和IRF - 1诱导的基因表达,并能使NIH3T3细胞或大鼠1细胞发生转化。此外,在BCBL - 1细胞中表达vIRF的反义RNA会导致某些HHV - 8基因的表达受到抑制,这表明vIRF也可能正向调节基因表达。我们证明,当通过GAL4 DNA结合结构域将vIRF导向DNA时,它可激活转录。单独无法激活转录的GAL - vIRF截短构建体在共转染入HeLa细胞时可协同进行反式激活,这表明vIRF的多个区域参与反式激活。这些研究拓宽了vIRF的潜在作用机制,使其包括转录激活以及转录抑制。