Adenovirus entry: Stability, uncoating, and nuclear import,Molecular Microbiology

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Adenovirus entry: Stability, uncoating, and nuclear import
Molecular Microbiology ( IF 2.6 ) Pub Date : 2022-04-17 , DOI: 10.1111/mmi.14909
Urs F Greber ₁ , Maarit Suomalainen ₁

Affiliation

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.

中文翻译：

腺病毒进入：稳定性、脱壳和核输入

腺病毒 (AdV) 在脊椎动物中广泛存在。它们感染呼吸道和胃肠道、眼睛、心脏、肝脏和肾脏，对免疫抑制的人来说是致命的。感染哺乳动物的乳腺腺病毒包括数百种不同类型，其中许多专门感染人类。人类腺病毒是临床应用中使用最广泛的载体，包括癌症治疗和 COVID-19 疫苗接种。AdV 载体在物理和遗传上是稳定的，对人类通常是安全的。这些颗粒具有二十面体外壳和带有 DNA 基因组的核蛋白核心。我们描述了 AdV 细胞进入的概念，并强调了病毒 DNA 的细胞质转运、脱壳和核导入方面的最新进展。我们强调了最近发现的病毒体蛋白 V 的“关键”功能，可确保细胞质颗粒的稳定性，在 E3 泛素连接酶 Mind bomb 1 (MIB1) 和蛋白酶体触发破坏的提示下，它在核孔复合体处松弛。驱动蛋白运动蛋白和微管对衣壳的破坏使关键蛋白暴露，并使蛋白 V 成为 MIB1 泛素化的靶标，从而使 V 与病毒 DNA 分离并增强 DNA 核输入。这些进展揭示了控制衣壳稳定性和过早脱壳的机制，并提供了对核酸核转运的深入了解。

更新日期：2022-04-17

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