Transcriptional activation of the interleukin-2 promoter by hepatitis C virus core protein
Transcriptional activation of the interleukin-2 promoter by hepatitis C virus core protein
复制标题
DOI：
10.1128/jvi.75.2.772-781.2001
复制
发表时间：
2001-01-01
影响因子：
5.4
通讯作者：
Rice, CM
中科院分区：
文献类型：
--
作者：
Bergqvist, A;Rice, CM
大多数丙型肝炎病毒(丙型肝炎病毒)感染者成为慢性携带者。有效地建立持续感染的病毒必须有有效的方法来逃避宿主防御。就丙型肝炎而言，人们对慢性感染是如何建立或维持的知之甚少。除了肝细胞，一些报道表明，丙型肝炎病毒可以感染T和B淋巴细胞。由于T细胞是病毒清除的关键，丙型肝炎病毒对T细胞功能的直接或间接影响可能会影响感染的结局。鉴于T细胞的生长和分化需要细胞因子白介素2(IL-2)，我们询问丙型肝炎病毒是否可能调节IL-2的合成。在各种条件下，部分丙型肝炎病毒多聚蛋白在Jurkat细胞中表达。我们发现，高度保守的丙型肝炎病毒核心蛋白，与其他刺激相结合，能够显著激活IL-2启动子的转录。这一活性需要核心蛋白的羧基末端疏水部分。活化依赖于活化T细胞的核因子(NFAT)，发生在酪氨酸激酶p56(Lck)缺陷的细胞中，并可被环孢素A和钙耗竭所阻断。这些结果表明，丙型肝炎病毒核心蛋白可以通过NFAT途径激活IL-2启动子的转录。这种新的活动可能会对T细胞的发育和持续性感染的建立产生影响。
Most patients infected with hepatitis C virus (HCV) become chronic carriers. Viruses that efficiently establish persistent infections must have effective ways of evading host defenses. In the case of HCV, little is known about how chronic infections are established or maintained. Besides hepatocytes, several reports suggest that HCV can infect T and B lymphocytes. Since T cells are essential for viral clearance, direct or indirect effects of HCV on T-cell function could influence the outcome of infection. Given that T-cell growth and differentiation require the cytokine interleukin 2 (IL-2), we asked whether HCV might modulate synthesis of IL-2. Portions of the HCV polyprotein were expressed in Jurkat cells under a variety of conditions. We found that the highly conserved HCV core protein, in combination with other stimuli, was able to dramatically activate transcription from the IL-2 promoter. The carboxy-terminal hydrophobic portion of the core protein was required for this activity. Activation was dependent on nuclear factor of activated T cells (NFAT), occurred in cells deficient in the tyrosine kinase p56(lck), and could be blocked by addition of cyclosporin A and by depletion of calcium. These results suggest that the HCV core protein can activate transcription of the IL-2 promoter through the NFAT pathway. This novel activity may have consequences for T-cell development and establishment of persistent infections.