Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Mol Microbiol. 2022 Oct;118(4):309-320. doi: 10.1111/mmi.14909. Epub 2022 Apr 26.
Adenoviruses (AdVs) are widespread in vertebrates. They infect the respiratory and gastrointestinal tracts, the eyes, heart, liver, and kidney, and are lethal to immunosuppressed people. Mastadenoviruses infecting mammals comprise several hundred different types, and many specifically infect humans. Human adenoviruses are the most widely used vectors in clinical applications, including cancer treatment and COVID-19 vaccination. AdV vectors are physically and genetically stable and generally safe in humans. The particles have an icosahedral coat and a nucleoprotein core with a DNA genome. We describe the concept of AdV cell entry and highlight recent advances in cytoplasmic transport, uncoating, and nuclear import of the viral DNA. We highlight a recently discovered "linchpin" function of the virion protein V ensuring cytoplasmic particle stability, which is relaxed at the nuclear pore complex by cues from the E3 ubiquitin ligase Mind bomb 1 (MIB1) and the proteasome triggering disruption. Capsid disruption by kinesin motor proteins and microtubules exposes the linchpin and renders protein V a target for MIB1 ubiquitination, which dissociates V from viral DNA and enhances DNA nuclear import. These advances uncover mechanisms controlling capsid stability and premature uncoating and provide insight into nuclear transport of nucleic acids.
腺病毒（AdVs）广泛存在于脊椎动物中。它们感染呼吸道和胃肠道、眼睛、心脏、肝脏和肾脏，对免疫抑制的人是致命的。感染哺乳动物的巨细胞病毒包含数百种不同类型，许多专门感染人类。人类腺病毒是临床应用中最广泛使用的载体，包括癌症治疗和 COVID-19 疫苗接种。AdV 载体在人体中物理和遗传上都很稳定，通常很安全。这些颗粒具有二十面体衣壳和核衣壳蛋白核心，带有 DNA 基因组。我们描述了 AdV 细胞进入的概念，并强调了细胞质运输、脱壳和病毒 DNA 核内输入的最新进展。我们强调了衣壳蛋白 V 的一个新发现的“关键”功能，它确保了细胞质颗粒的稳定性，而核孔复合物中的 E3 泛素连接酶 Mind bomb 1（MIB1）和蛋白酶体的信号会使其松弛，从而触发衣壳蛋白 V 的破坏。驱动蛋白马达蛋白和微管对衣壳的破坏暴露了关键蛋白 V，使其成为 MIB1 泛素化的靶标，从而使 V 从病毒 DNA 上解离，并增强 DNA 核内输入。这些进展揭示了控制衣壳稳定性和过早脱壳的机制，并为核酸的核内运输提供了深入的了解。
