Qin Di, Zeng Yi, Qian Chao, Huang Zan, Lv Zhigang, Cheng Lin, Yao Shuihong, Tang Qiao, Chen Xiuying, Lu Chun
Laboratory of Reproductive Medicine, Key Laboratory of Pathogen Biology of Jiangsu Province, and Department of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, China.
Cell Microbiol. 2008 Mar;10(3):713-28. doi: 10.1111/j.1462-5822.2007.01079.x. Epub 2007 Nov 27.
Previously, we identified that both human herpesvirus 6 and human immunodeficiency virus type 1 Tat were important cofactors that activated lytic cycle replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Here, we further investigated the potential of herpes simplex virus type 1 (HSV-1) to influence KSHV replication. We demonstrated that HSV-1 was a potentially important factor in the pathogenesis of Kaposi's sarcoma, 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 ORF50 and a luciferase reporter assay testing ORF50 promoter-driven luciferase activity. Finally, we discovered that production of human interleukin-10 (IL-10) and IL-4 partially contributed to HSV-1-induced KSHV replication. Our data present the first direct evidence that HSV-1 can activate KSHV lytic replication and suggest a role of HSV-1 in KSHV pathogenesis.
此前，我们已确定人类疱疹病毒6型和人类免疫缺陷病毒1型反式激活因子都是激活卡波西肉瘤相关疱疹病毒（KSHV）裂解周期复制的重要辅助因子。在此，我们进一步研究了单纯疱疹病毒1型（HSV-1）影响KSHV复制的可能性。我们证明，通过在BCBL-1细胞中产生裂解期mRNA转录本、病毒蛋白和传染性病毒颗粒来确定，HSV-1是卡波西肉瘤发病机制中一个潜在的重要因素。使用靶向KSHV ORF50的小干扰RNA进行的RNA干扰实验以及检测ORF50启动子驱动的荧光素酶活性的荧光素酶报告基因检测进一步证实了这些结果。最后，我们发现人类白细胞介素10（IL-10）和IL-4的产生部分促成了HSV-1诱导的KSHV复制。我们的数据首次提供了直接证据，表明HSV-1可激活KSHV裂解复制，并提示HSV-1在KSHV发病机制中的作用。
