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在现场的冷ET重新定义了HPV拆卸和运输范式

Renaldo Sutanto^1,2, Jaimin Rana^1,3, Billy Tsai^2,4

¹Life Sciences Institute, University of Michigan, Ann Arbor, MI 48108, United States.

bioRxiv : the preprint server for biology

|September 15, 2025

概括

人类乳头瘤病毒 (HPV) 在 lysosomes 和 Golgi 中保持完整,挑战以前的模型. 这种病毒使用COPI依赖的机制运输到细胞核,有结构性桥梁指导它的路径.

科学领域:

病毒学病毒学
细胞生物学细胞生物学
结构生物学结构生物学

背景情况:

人类乳头瘤病毒 (HPV) 是4.5%的人类癌症的原因.
没有完全理解HPV感染,拆卸和传输的细胞机制.
目前的模型表明,HPV在逆行运输过程中会发生分解.

研究的目的:

使用in situ冷电子断层扫描 (cryo-ET) 可视化HPV16感染周期.
为了研究HPV贩运和宿主细胞内的囊稳定性.
阐明HPV从戈尔吉细胞转移到细胞核的机制.

主要方法:

在现场冷电子断层扫描 (cryo-ET) 用于可视化高风险的HPV16.
在细胞区内感染周期期间直接可视化HPV.
分析病毒囊完整性和与细胞传输机械的关联.

主要成果:

在到达溶酶体后,HPV16仍然完好无损,具有感染能力,这与之前关于无活化的假设相矛盾.
与现有的模型相反,HPV囊在逆行运输到戈尔吉河时不会逐渐分解.
HPV通过COPI依赖的囊泡从Golgi芽传输,由可能涉及L2囊的蛋白质桥梁引导.

结论:

溶解体作为感染性HPV的储存库.
在逆行贩运期间HPV囊的稳定性是其感染周期的关键特征.
一个新的COPI-依赖机制,涉及结构桥梁,促进HPV向核的运输.

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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...