# Arrest of Viral Proliferation by Ectopic Copies of Its Cognate Replication Origin

**Authors:** Manuel S. Valenzuela, Chakradhari Sharan

PMC · DOI: 10.3390/genes6020436 · 2015-06-23

## TL;DR

Adding extra copies of a virus's DNA replication origin in bacteria can stop the virus from multiplying.

## Contribution

The study shows that ectopic viral origin copies can block viral DNA replication initiation.

## Key findings

- Ectopic λ origin copies in E. coli prevented normal viral DNA replication initiation.
- Host growth and viral production were reduced in the presence of decoy origins.
- Electron microscopy confirmed altered replicative intermediates in infected cells.

## Abstract

The initiation step of DNA replication is the crucial determinant of proliferation in all organisms. This step depends on the specific interaction of DNA sequences present at origins of DNA replication and their cognate activators. We wished to explore the hypothesis that the presence of ectopic origin copies may interfere with proper genome duplication. Bacteriophage λ was used as a model system. To this end, the outcome of an infection of an E. coli strain harboring ectopic copies of the λ origin region was analyzed. By measuring the effect on the host growth, viral production, and electro-microscopic visualization of the resulting λ replicative intermediates, we concluded that the ectopic copies had prevented the normal initiation step of λ DNA replication. These results suggest that DNA decoys encoding viral origins could constitute effective tools to specifically arrest viral proliferation.

## Linked entities

- **Species:** Escherichia coli (taxon 562)

## Full-text entities

- **Diseases:** HBT (MESH:C562908), bacteria (MESH:C000719206), Infection (MESH:D007239)
- **Chemicals:** thymidine (MESH:D013936), 14N (-), nitrogen (MESH:D009584), KOH (MESH:C029943), 2H (MESH:D003903), NaCl (MESH:D012965), CsCl (MESH:C028019), H2O (MESH:D014867), 3H (MESH:D014316), TCA (MESH:D014238), KCN (MESH:D011190), KCl (MESH:D011189), O (MESH:D010100), pyridine (MESH:C023666), sarkosyl (MESH:C025231), EDTA (MESH:D004492), D2O (MESH:D017666), DTT (MESH:D004229), MgSO4 (MESH:D008278), HCl (MESH:D006851), MgCl2 (MESH:D015636), Hepes (MESH:D006531), ethanol (MESH:D000431), ice (MESH:D007053), ether (MESH:D004986), agar (MESH:D000362), maltose (MESH:D008320), TM (MESH:D013932)
- **Species:** Escherichia coli HB101 (strain) [taxon 634468], Homo sapiens (human, species) [taxon 9606], Escherichia coli K-12 (strain) [taxon 83333], Lambdavirus lambda (species) [taxon 10710], Escherichia coli (E. coli, species) [taxon 562]
- **Cell lines:** CR34 — Cairina moschata (Muscovy duck), Transformed cell line (CVCL_S509), HB101 — Mus musculus (Mouse), Hybridoma (CVCL_J815), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), pOri1 — Mus musculus (Mouse), Hybridoma (CVCL_C7RB), HBT — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_D281)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4488673/full.md

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Source: https://tomesphere.com/paper/PMC4488673