Körner H, Fritzsche U, Burgert H G
Max-Planck-Institut für Immunobiologie, Spemann Laboratories, Freiburg, Germany.
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11857-61. doi: 10.1073/pnas.89.24.11857.
Human adenovirus (Ad) can cause persistent infections in humans. Early region 3 (E3) of the virus appears to be implicated in this phenomenon. This transcription unit encodes proteins that interfere in various ways with host cell functions, including (i) cell-surface expression of histocompatibility class I antigens (HLA), (ii) cell-surface expression of the epidermal growth factor receptor (EGF-R), and (iii) the biological activity of tumor necrosis factor alpha (TNF-alpha). We transfected the human cell line 293 with the entire E3 region of Ad2 and investigated the influence of the cytokines TNF-alpha and interferon gamma (IFN-gamma) on cell-surface expression of HLA class I and the EGF-R. Whereas IFN-gamma treatment induced expression of HLA to some extent but not that of the EGF-R, TNF-alpha treatment augmented the reduction of these cell-surface molecules. Subsequent studies on the mechanism of this effect showed a TNF-alpha-dependent upregulation of E3 protein (E3/19K) and mRNA. The significance of this phenomenon was confirmed in infection experiments. A dramatic increase in the amount of E3/19K, even after short induction with low doses of TNF-alpha could be demonstrated. The study provides evidence for an interaction between the immune system and Ad in which the virus takes advantage of an immune mediator to escape immunosurveillance of the host.
人腺病毒（Ad）可在人体内引起持续性感染。该病毒的早期区域3（E3）似乎与这一现象有关。这个转录单元编码的蛋白质以多种方式干扰宿主细胞功能，包括：（i）主要组织相容性复合体I类抗原（HLA）的细胞表面表达；（ii）表皮生长因子受体（EGF-R）的细胞表面表达；以及（iii）肿瘤坏死因子α（TNF-α）的生物学活性。我们用Ad2的整个E3区域转染了人细胞系293，并研究了细胞因子TNF-α和干扰素γ（IFN-γ）对HLA I类和EGF-R细胞表面表达的影响。虽然IFN-γ处理在一定程度上诱导了HLA的表达，但未诱导EGF-R的表达，而TNF-α处理增强了这些细胞表面分子的减少。随后对这种效应机制的研究表明，TNF-α依赖性上调了E3蛋白（E3/19K）和mRNA。在感染实验中证实了这一现象的重要性。即使在用低剂量TNF-α短暂诱导后，也能证明E3/19K的量有显著增加。该研究为免疫系统与腺病毒之间的相互作用提供了证据，即病毒利用一种免疫介质来逃避宿主的免疫监视。
