Tsui L V, Guidotti L G, Ishikawa T, Chisari F V
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12398-402. doi: 10.1073/pnas.92.26.12398.
Using transgenic mice that replicate the hepatitis B virus (HBV) genome, we recently demonstrated that class I-restricted, hepatitis B surface antigen-specific cytotoxic T lymphocytes (CTLs) can noncytolytically eliminate HBV pregenomic and envelope RNA transcripts from the hepatocyte. We now demonstrate that the steady-state content of these viral transcripts is profoundly reduced in the nucleus and cytoplasm of CTL-activated hepatocytes, but their transcription rates are only slightly reduced. Additionally, we demonstrate that transcripts covering the HBV X coding region are resistant to downregulation by the CTL. These results imply the existence of CTL-inducible hepatocellular factors that interact with a discrete element(s) between nucleotides 3157 and 1239 within the viral pregenomic and envelope transcripts and mediate their degradation, thus converting the hepatocyte from a passive victim to an active participant in the host response to HBV infection.
利用复制乙型肝炎病毒（HBV）基因组的转基因小鼠，我们最近证明，I类限制性、乙型肝炎表面抗原特异性细胞毒性T淋巴细胞（CTL）可通过非细胞溶解方式从肝细胞中清除HBV前基因组和包膜RNA转录本。我们现在证明，在CTL激活的肝细胞的细胞核和细胞质中，这些病毒转录本的稳态含量显著降低，但其转录速率仅略有降低。此外，我们证明，覆盖HBV X编码区的转录本对CTL的下调具有抗性。这些结果表明，存在CTL诱导的肝细胞因子，它们与病毒前基因组和包膜转录本中核苷酸3157至1239之间的离散元件相互作用并介导其降解，从而使肝细胞从HBV感染宿主反应中的被动受害者转变为积极参与者。
