ウイルスがDNAを保護する仕組みを解明、新たな抗菌戦略の可能性(Virus Infects Cells with a Protective Cloaking Mechanism)

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2025-04-02 カリフォルニア大学サンディエゴ校

カリフォルニア大学サンディエゴ校の研究チームは、バクテリオファージ(細菌に感染するウイルス)の一種である「ジャンボファージ」が、感染初期にEPI(Early Phage Infection)小胞と呼ばれる膜構造を形成し、ウイルスのゲノムを細菌の免疫系から隠すことを発見しました。このEPI小胞は、ウイルスが細菌内で核を形成する際に重要な役割を果たし、細菌の防御機構を回避する手助けをします。この知見は、抗生物質耐性菌に対する新しいファージ療法の開発に寄与する可能性があります。

<関連情報>

細胞膜とタンパク質が結合した小器官がファージ感染時にゲノムを区画化することを発見 Sequential membrane- and protein-bound organelles compartmentalize genomes during phage infection

Emily G. Armbruster, Phoolwanti Rani, Jina Lee, Niklas Klusch, Joshua Hutchings, Lizbeth Y. Hoffman, Hannah Buschkaemper, Eray Enustun, Benjamin A. Adler, Koe Inlow, Arica R. VanderWal, Madelynn Y. Hoffman, Daksh Daksh, Ann Aindow, Amar Deep, Zaida K. Rodriguez, Chase J. Morgan, Majid Ghassemian, Thomas G. Laughlin, Emeric Charles…Joe Pogliano
Cell Host & Microbe  Published: March 31, 2025
DOI:https://doi.org/10.1016/j.chom.2025.03.005

Graphical abstract

ウイルスがDNAを保護する仕組みを解明、新たな抗菌戦略の可能性(Virus Infects Cells with a Protective Cloaking Mechanism)

Highlights

  • The phage nucleus is essential for Chimalliviridae genome replication
  • The phage nucleus is preceded by the early phage infection (EPI) vesicle
  • The EPI vesicle is a transcriptionally active, membrane-bound organelle

Summary

Many eukaryotic viruses require membrane-bound compartments for replication, but no such organelles are known to be formed by prokaryotic viruses. Bacteriophages of the Chimalliviridae family sequester their genomes within a phage-generated organelle, the phage nucleus, which is enclosed by a lattice of the viral protein ChmA. We show that inhibiting phage nucleus formation arrests infections at an early stage in which the injected phage genome is enclosed within a membrane-bound early phage infection (EPI) vesicle. Early phage genes are expressed from the EPI vesicle, demonstrating its functionality as a prokaryotic, transcriptionally active, membrane-bound organelle. We also show that the phage nucleus is essential, with genome replication beginning after the injected DNA is transferred from the EPI vesicle to the phage nucleus. Our results show that Chimalliviridae require two sophisticated subcellular compartments of distinct compositions and functions that facilitate successive stages of the viral life cycle.

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