Scientists Design the First Synthetic Virus Infection Cycle
French and American research teams have succeeded in reproducing a complete infection cycle between a bacteriophage, a virus that infects bacteria, and a synthetic host cell. Their achievement opens new possibilities for fundamental research and biotechnological applications.
Viruses and the cells they infect have diversified through evolution. This diversity means that there is a large variety of mechanisms for invading cells. Yet all viruses follow a set of universal steps: they identify the cell they can invade, release their genetic material inside the host cell, hijack its machinery to produce their offspring, and finally lyse, break down the cell to release the new viral particles.
“Viruses do not think. They are encoded with the ability to open a door. Previous studies have shown that if we present them with the right door, they open it,” explained Ariel Lindner, Research Director at Inserm and Sorbonne University, whose research lies at the interface between systems and synthetic biology.
This led him and Vincent Noireaux, professor at the University of Minnesota, United States, to the following question: could a virus infect a system that does not exist in nature? In other words, could a virus bind to and inject its DNA into a synthetic system to which they had attached the right door?
A bacteriophage, a synthetic cell, and a door
For this experiment, published in Nature Communications, researchers chose bacteriophages. “Bacteriophage, or simply phages, are the most abundant viruses on Earth. They are specific to micro-organisms, particularly bacteria, and their interactions with host cells are simpler than those of viruses that infect humans, such as SARS-CoV-2 or HIV,” stressed Vincent Noireaux. “They are also essential to ecosystems.”
The Noireaux Lab specialises in cell-free gene expression systems, i.e., systems capable of reading DNA to produce RNA or protein molecules. For the virus’s host, they designed ‘synthetic cells’, in this case, liposomes the size of living cells, encapsulating a cell-free gene expression system. Simpler than that of a natural cell, their membrane consisted of a simple phospholipid bilayer, to which the researchers attached fatty sugars (lipopolysaccharides), the virus’s entry point.
Reproducing the universal steps of infection
“We created a simple system, where not everything works as it does in living systems, but which captures the universal steps of infection,” explained Antoine Levrier, first author of the study.
He continued: “We attached a door, the lipopolysaccharides, which remained stable on the outer layer of the synthetic cell and could be recognised by the phage. The phage bound to it and formed a channel to release its 60-gene genome into the synthetic cell. Inside, these genes were replicated and expressed, leading to the assembly of new phage particles. The newly formed particles were then released by osmotic shock.”
An engineering challenge with numerous constraints
The conception of the infection cycle required integrating multiple steps, each with its own constraints. The challenge was not just identifying the appropriate components and methods. The steps had to be executed flawlessly and within time limits. “It required Antoine’s talent to make this work,” emphasised Ariel Lindner and Vincent Noireaux.
Next steps
Scientists have managed to design the first synthetic cell phage cycle. The teams are currently studying this system, as some of the mechanisms used by bacteriophages to infect their synthetic cells remain unclear.
“We have shown that phages can work outside natural systems,” said Vincent Noireaux. “But because this is so far from nature, we still do not understand, for example, how the phage genome enters the cell across the synthetic membrane.”
Exploring and exploiting: what we can learn from reconstructing a viral infection
The researchers believe that once fully understood, the system could be adapted to other phages and used as a platform to study viral mechanisms or harness phages to obtain results that cannot be achieved under natural conditions.
“Phages have been very helpful in deciphering the main tenets of molecular biology and are widely used in biotechnology to find new proteins. Reconstituting their advantages in a synthetic system opens up possibilities that living cells cannot offer,” added Ariel Lindner.
Researchers hope that other laboratories will adopt this system and work together to explore and exploit the interactions between synthetic systems and viruses.
Scientific publication:
A synthetic cell phage cycle
Antoine Levrier, Paul Soudier, David Garenne, Ziane Izri, Steven Bowden, Ariel B. Lindner and Vincent Noireaux
Nature Communications 17, Article number 557 (2026)