Forero Adriana, McCormick Kevin D, Jenkins Frank J, Sarkar Saumendra N
Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, USA.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Virology. 2014 Jun;458-459:4-10. doi: 10.1016/j.virol.2014.04.020. Epub 2014 May 5.
Primary effusion lymphoma (PEL), associated with the latent infection by KSHV, constitutively expresses interferon-regulatory factor 4 (IRF4). We recently showed that IRF4 differentially regulates expression of cellular interferon-stimulated genes (ISGs) and viral genes (Forero et al., 2013). Here, using inducible IRF4 knockdown, we demonstrate that IRF4 silencing results in enhanced transcription of KSHV replication transactivator RTA. As a result viral transcription is increased leading to virus reactivation. Taken together, our results show that IRF4 helps maintain the balance between latency and KSHV reactivation in PEL cells.
原发性渗出性淋巴瘤（PEL）与卡波西肉瘤相关疱疹病毒（KSHV）的潜伏感染有关，持续性表达干扰素调节因子4（IRF4）。我们最近发现，IRF4对细胞干扰素刺激基因（ISG）和病毒基因的表达具有差异调节作用（Forero等人，2013年）。在此，我们通过诱导性IRF4敲低实验证明，IRF4沉默会导致KSHV复制反式激活因子RTA的转录增强。结果，病毒转录增加，导致病毒重新激活。综上所述，我们的结果表明，IRF4有助于维持PEL细胞中潜伏状态与KSHV重新激活之间的平衡。
