Sequential membrane- and protein-bound organelles compartmentalize genomes during phage infection
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.
Authors
- Jina Lee (ORCID: https://orcid.org/0000-0002-7808-1045)
- Joshua Hutchings (ORCID: https://orcid.org/0000-0001-6841-8583)
- Eray Enüstün (ORCID: https://orcid.org/0000-0001-7550-7752)
- Joe Pogliano (ORCID: https://orcid.org/0000-0001-8989-2655)
- Chase J. Morgan (ORCID: https://orcid.org/0000-0002-7498-8678)
- Phoolwanti Rani (ORCID: https://orcid.org/0000-0002-6731-9003)
- Zaida K. Rodriguez (ORCID: https://orcid.org/0000-0003-0447-533X)
- David F. Savage (ORCID: https://orcid.org/0000-0003-0042-2257)
- Majid Ghassemian (ORCID: https://orcid.org/0000-0003-1026-5152)
- Kevin D. Corbett (ORCID: https://orcid.org/0000-0001-5854-2388)
- Thomas G. Laughlin (ORCID: https://orcid.org/0000-0001-8943-1330)
- Emeric Charles (ORCID: https://orcid.org/0000-0002-3465-5625)
- Arica R VanderWal
- Kit Pogliano (ORCID: https://orcid.org/0000-0002-7868-3345)
- Koe Inlow (ORCID: https://orcid.org/0000-0002-2535-9613)
- Brady F. Cress (ORCID: https://orcid.org/0000-0002-2948-2846)
- Ann Aindow (ORCID: https://orcid.org/0000-0001-8821-9493)
- Emily G. Armbruster (ORCID: https://orcid.org/0000-0003-0377-1209)
- Jennifer A. Doudna (ORCID: https://orcid.org/0000-0001-9161-999X)
- Amar Deep (ORCID: https://orcid.org/0000-0003-2003-2889)
- N. Klusch (ORCID: https://orcid.org/0000-0003-2459-7377)
- Maureane Hoffman (ORCID: https://orcid.org/0000-0001-7123-0100)
- Elizabeth Villa (ORCID: https://orcid.org/0000-0003-4677-9809)
- Benjamin A. Adler (ORCID: https://orcid.org/0000-0002-7488-3040)
- Lloyd A. Hoffman (ORCID: https://orcid.org/0009-0008-5718-2323)
- Daksh Daksh
- Hannah Buschkaemper
Institutions
- QB3 (US)
- National Institute of Science Education and Research (IN)
- University of California San Diego (US)
- Abterra Biosciences (United States) (US)
- Innovative Genomics Institute (US)
- University of California San Diego Medical Center (US)
- Ludwig-Maximilians-Universität München (DE)
- University of California, Berkeley (US)
Publication Details
- Journal
- Cell Host & Microbe
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1016/j.chom.2025.03.005
- Citations
- 17
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 29.18