Burgert H G, Ruzsics Z, Obermeier S, Hilgendorf A, Windheim M, Elsing A
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Genzentrum der Ludwig-Maximilians-Universität, Feodor-Lynen-Str. 25, 81377 München, Germany.
Curr Top Microbiol Immunol. 2002;269:273-318. doi: 10.1007/978-3-642-59421-2_16.
Adenoviruses (Ads) cause acute and persistent infections. Alike the much more complex herpesviruses, Ads encode numerous immunomodulatory functions. About a third of the viral genome is devoted to counteract both the innate and the adaptive antiviral immune response. Immediately upon infection, E1A blocks interferon-induced gene expression and the VA-RNA inhibits interferon-induced PKR activity. At the same time, E1A reprograms the cell for DNA synthesis and induces the intrinsic cellular apoptosis program that is interrupted by E1B/19K and E1B/55K proteins, the latter inhibits p53-mediated apoptosis. Most other viral stealth functions are encoded by a separate transcription units, E3. Several E3 products prevent death receptor-mediated apoptosis. E3/14.7K seems to interfere with the cytolytic and pro-inflammatory activities of TNF while E3/10.4K and 14.5K proteins remove Fas and TRAIL receptors from the cell surface by inducing their degradation in lysosomes. These and other functions that may afect granule-mediated cell death might drastically limit lysis by NK cells and cytotoxic T cells (CTL). Moreover, Ads interfere with recognition of infected cell by CTL. The paradigmatic E3/19K protein subverts antigen presentation by MHC class I molecules by inhibiting their transport to the cell surface. In concert, these viral countermeasures ensure prolonged survival in the infected host and, as a consequence, facilitate transmission. Elucidating the molecular mechanisms of Ad-mediated immune evasion has stimulated corresponding research on other viruses. This knowledge will also be instrumental for designing better vectors for gene therapy and vaccination, and may lead to a more rational treatment of life-threatening Ad infections, e.g. in transplantation patients.
腺病毒可引起急性和持续性感染。与更为复杂的疱疹病毒一样，腺病毒编码多种免疫调节功能。病毒基因组约三分之一用于对抗先天性和适应性抗病毒免疫反应。感染后，E1A立即阻断干扰素诱导的基因表达，而VA-RNA抑制干扰素诱导的PKR活性。同时，E1A对细胞进行重编程以进行DNA合成，并诱导被E1B/19K和E1B/55K蛋白中断的内在细胞凋亡程序，后者抑制p53介导的凋亡。大多数其他病毒的隐匿功能由一个单独的转录单元E3编码。几种E3产物可防止死亡受体介导的凋亡。E3/14.7K似乎干扰肿瘤坏死因子的细胞溶解和促炎活性，而E3/10.4K和14.5K蛋白通过诱导其在溶酶体中的降解，从细胞表面去除Fas和TRAIL受体。这些以及其他可能影响颗粒介导的细胞死亡的功能，可能会极大地限制自然杀伤细胞和细胞毒性T细胞（CTL）的裂解作用。此外，腺病毒干扰CTL对感染细胞的识别。典型的E3/19K蛋白通过抑制MHC I类分子向细胞表面的转运，破坏抗原呈递。这些病毒对策共同确保在感染宿主中延长存活时间，从而促进传播。阐明腺病毒介导的免疫逃逸分子机制，激发了对其他病毒的相应研究。这些知识对于设计更好的基因治疗和疫苗载体也将有帮助，并可能导致对危及生命的腺病毒感染（如移植患者中的感染）进行更合理的治疗。
