Jiang H, Wang Z, Serra D, Frank M M, Amalfitano A
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Mol Ther. 2004 Dec;10(6):1140-2. doi: 10.1016/j.ymthe.2004.08.015.
Recombinant adenoviruses are one of the most common gene transfer vectors utilized in human clinical trials, but it is also clear that systemic administration of this virus will be met by host innate and adaptive antiviral immune responses. One element of innate immunity is the complement system, a group of proteins that has evolved to rapidly recognize foreign microbes and viruses and to clear them from the circulatory system prior to their gaining entry to vulnerable host cells. Excessive complement activation can initiate or propagate a number of deleterious inflammatory responses, by release of potent cytokines and anaphylatoxins and/or by direct cellular toxicity. These reactions can progress rapidly and are factors important in serious complications, including the systemic inflammatory response syndrome and the adult respiratory distress syndrome.
重组腺病毒是人类临床试验中最常用的基因转移载体之一，但很明显，这种病毒的全身给药会遭遇宿主先天性和适应性抗病毒免疫反应。先天性免疫的一个要素是补体系统，这是一组进化而来的蛋白质，可快速识别外来微生物和病毒，并在它们进入易受攻击的宿主细胞之前将其从循环系统中清除。补体的过度激活可通过释放强效细胞因子和过敏毒素和/或通过直接细胞毒性引发或传播一些有害的炎症反应。这些反应可迅速发展，是严重并发症（包括全身炎症反应综合征和成人呼吸窘迫综合征）中的重要因素。
