KAPOSIS SARCOMA ASSOCIATED HERPESVIRUS VIRAL INTERFERON REGULATORY FACTOR

干扰素(IFN)是一类多功能细胞因子家族，具有 卡波西K9开放阅读框架的抗病毒活性 肉瘤相关疱疹病毒(KSHV)具有显著的同源性 利用细胞干扰素调节因子(IRF)，我们研究了 干扰素介导信号中K9表达的功能结果 K9的转导表达显著抑制转录 干扰素-`、--诱导的激活，以及-进一步，它诱导 NIH 3T3细胞转化，导致形态变化， 病灶的形成和生长在低血清条件下的表达 KSHV感染BCBL-1细胞中反义K9的表达持续增加 干扰素介导的转录激活，但显著降低了 KSHV基因的表达因此，KSHV的K9基因编码 第一个病毒编码的IRF(v-IRF)，起到抑制因子的作用 细胞内干扰素介导的信号转导此外，v-IRF可能 在调节KS-HV基因表达方面发挥了重要作用 结果表明，KSHV通过一种独特的机制拮抗 携带功能性v-IRF的干扰素抗病毒活性 出版物：李，M，李，H，郭，J，内佩尔，F，Fleckenstein，B Ozato，K和Jung，Ju Kaposi的肉瘤相关疱疹病毒 干扰素调节因子J Virol 1998；72：5433-5440

Interferons (IFNs) are a family of multifunctional cytokines with antiviral activities The K9 open reading frame of Kaposi's sarcoma-associated herpesvirus (KSHV) exhibits significant homology with cellular IFN regulatory factors (IRFs) We have investigated the functional consequence of K9 expression in IFN-mediated signal transduction Expression of K9 dramatically repressed transcriptional activation induced by IFN-`, - , and - Further, it induced transformation of NIH 3T3 cells, resulting in morphologic changes, focus formation, and growth in reduced-serum conditions The expression of antisense K9 in KSHV-infected BCBL-1 cells consistently increased IFN-mediated transcriptional activation but drastically decreased the expression of certain KSHV genes Thus, the K9 gene of KSHV encodes the first virus-encoded IRF (v-IRF) which functions as a repressor for cellular IFN-mediated signal transduction In addition, v-IRF likely plays an important role in regulatin g KS HV gene expression These results suggest that KSHV employs an unique mechanism to antagonize IFN-mediated antiviral activity by harboring a functional v-IRF PUBLICATIONS Li, M , Lee, H, Guo, J, Neipel, F, Fleckenstein, B, Ozato, K, and Jung, JU Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor J Virol 1998; 72:5433-5440