Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Department of Molecular Biology, Princeton University, NJ, USA.
FEBS Lett. 2019 Dec;593(24):3395-3418. doi: 10.1002/1873-3468.13700. Epub 2019 Dec 20.
Animal viruses are well recognized for their ability to uncover fundamental cell and molecular processes, and adenovirus certainly provides a prime example. This review illustrates the lessons learned from studying adenovirus over the past five decades. We take a look back at the key studies of adenovirus structure and biophysical properties, which revealed the mechanisms of adenovirus association with antibody, cell receptor, and immune molecules that regulate infection. In addition, we discuss the critical contribution of studies of adenovirus gene expression to elucidation of fundamental reactions in pre-mRNA processing and its regulation. Other pioneering studies furnished the first examples of protein-primed initiation of DNA synthesis and viral small RNAs. As a nonenveloped virus, adenoviruses have furnished insights into the modes of virus attachment, entry, and penetration of host cells, and we discuss the diversity of cell receptors that support these processes, as well as membrane penetration. As a result of these extensive studies, adenovirus vectors were among the first to be developed for therapeutic applications. We highlight some of the early (unsuccessful) trials and the lessons learned from them.
动物病毒以揭示基本的细胞和分子过程的能力而闻名,腺病毒无疑提供了一个很好的例子。这篇综述展示了过去五十年研究腺病毒所获得的经验教训。我们回顾了腺病毒结构和生物物理特性的关键研究,这些研究揭示了腺病毒与抗体、细胞受体和调节感染的免疫分子结合的机制。此外,我们还讨论了研究腺病毒基因表达对阐明前体 RNA 加工及其调控的基本反应的重要贡献。其他开创性的研究提供了蛋白质引发 DNA 合成和病毒小 RNA 的第一个例子。作为一种无包膜病毒,腺病毒为病毒附着、进入和穿透宿主细胞的方式提供了见解,我们讨论了支持这些过程的细胞受体的多样性,以及膜穿透。由于这些广泛的研究,腺病毒载体是最早被开发用于治疗应用的载体之一。我们强调了一些早期(不成功)的试验及其从中吸取的教训。