HIV-1相关炎性细胞因子诱导人血管内皮细胞中潜伏感染KSHV的溶解性周期复制  

Reactivation of latent Kaposi′s sarcoma-associated herpesvirus in human umbilical vein endothelial cells by HIV-1-related inflammatory cytokines

作　　者：卢春[1] 唐桂霞[1] 曾怡[1] 钱超[1] 秦娣[1] 

机构地区：[1]南京医科大学微生物学与免疫学系,210029

出　　处：《中华微生物学和免疫学杂志》2005年第11期880-884,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金项目(30100160和30271179);教育部留学回国人员科研启动基金

摘　　要：目的研究HIV21感染相关炎症细胞因子是否能够激活人脐静脉血管内皮细胞(HUVEC)中潜伏感染的卡波济肉瘤相关疱疹病毒(KSHV);探讨该激活作用是否由KSHVRta基因所介导。方法采用体外模拟系统,研究了与HIV-1感染T细胞诱生的细胞因子相似的重组人细胞因子对HUVEC中潜伏感染的KSHV复制的影响。通过Northernblot和定量PCR检测ORF26(该基因编码的病毒次要衣壳蛋白仅在KSHV被激活时表达)mRNA表达来分析KSHV的激活。运用KSHVRta基因启动子(KSHV复制时最先被激活的启动子)驱动的虫荧光素酶报告基因进一步证实并扩展研究结果。结果包括干扰素-γ(IFN2γ)、肝细胞生长因子P扩散因子(HGFPSF)及制瘤蛋白M(oncostatinM,OSM)在内的重组细胞因子不仅可诱导HUVEC中潜伏感染的KSHV发生溶解性周期复制,而且能增强Rta启动子活性。结论HIV-1感染相关的炎性细胞因子是诱导HUVEC中KSHV溶解性周期复制的因素,而且该过程至少有部分由KSHV的Rta启动子介导。Objective To determine whether HIV-1-related inflammatory cytokines can activate lytie cycle replication of Kaposi＇s sareoma-asseciated herpesvirus（KSHV） in human umbilical vein endothelial cells（ HUVEC） and to investigate its potential role in Rta promoter of KSHV involved in reactivation. Methods Using an in vitro model system, we examined the effect of recombinant human cytokines that were similar to that produced by HIV-1-infected T cells on KSHV replication in latently infected HUVEC. KSHV reactivation was analyzed with Northern blot analysis and quantitative PCR for ORF26 mRNA expression, a gene encoding the KSHV minor capsid protein was only activated during reactivation. The results were extended and confirmed using a luciferase reporter construct driven by the KSHV Rta（ replication and transcription activator） promoter, the first promoter activated during KSHV replication. Results Recombinant cyto-kines, such as gamma interferon（IFN-γ）, hepatocyte growth factor/scatter factor （HGF/SF）, and oncostatin M（OSM） not only induce KSHV lyric cycle replication, but also sfimnlate Rta promoter activity in latenfly infected HUVECs. Condusion HIV-1-related inflammatory cytokines are responsible for the induction of KSHV lyric cycle replication in HUVEC and the induction may be, at least in oart, mediated bv Rta promoter of KSHV.

关 键 词：细胞因子 卡波济肉瘤相关疱疹病毒 复制和转录激活蛋白 

分 类 号：R373[医药卫生—病原生物学]