Department of Immunology and Microbiology, University of California, San Francisco, San Francisco, CA 94158, USA.
J. David Gladstone Institutes, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell Host Microbe. 2024 Jul 10;32(7):1050-1058.e7. doi: 10.1016/j.chom.2024.05.016. Epub 2024 Jun 12.
Viral genomes are most vulnerable to cellular defenses at the start of the infection. A family of jumbo phages related to phage ΦKZ, which infects Pseudomonas aeruginosa, assembles a protein-based phage nucleus to protect replicating phage DNA, but how it is protected prior to phage nucleus assembly is unclear. We find that host proteins related to membrane and lipid biology interact with injected phage protein, clustering in an early phage infection (EPI) vesicle. The injected virion RNA polymerase (vRNAP) executes early gene expression until phage genome separation from the vRNAP and the EPI vesicle, moving into the nascent proteinaceous phage nucleus. Enzymes involved in DNA replication and CRISPR/restriction immune nucleases are excluded by the EPI vesicle. We propose that the EPI vesicle is rapidly constructed with injected phage proteins, phage DNA, host lipids, and host membrane proteins to enable genome protection, early transcription, localized translation, and to ensure faithful genome transfer to the proteinaceous nucleus.
病毒基因组在感染开始时最容易受到细胞防御的攻击。一类与感染铜绿假单胞菌的噬菌体 ΦKZ 相关的巨型噬菌体，组装了一个基于蛋白质的噬菌体核来保护复制的噬菌体 DNA，但在噬菌体核组装之前它是如何被保护的尚不清楚。我们发现，与膜和脂质生物学相关的宿主蛋白与注入的噬菌体蛋白相互作用，聚集在早期噬菌体感染 (EPI) 小泡中。注入的病毒粒子 RNA 聚合酶 (vRNAP) 执行早期基因表达，直到噬菌体基因组与 vRNAP 和 EPI 小泡分离，进入新生的蛋白噬菌体核。参与 DNA 复制和 CRISPR/限制免疫核酸酶的酶被 EPI 小泡排除在外。我们提出，EPI 小泡是通过注入的噬菌体蛋白、噬菌体 DNA、宿主脂质和宿主膜蛋白快速构建的，以实现基因组保护、早期转录、局部翻译，并确保将忠实的基因组转移到蛋白核。
