New research shows that viruses are using information from their environment to decide when to sit tightly inside their host and when to multiply and kill the host cell. Right now, viruses are exploiting the ability to monitor their environment to their advantage. But in the future, ‘we may exploit this to their detriment,’ said one writer.
A virus’s ability to sense its environment, including elements produced by its host, adds “another layer of complexity to viral-host interactions,” says Evan Aril, professor of biological sciences and senior author on the new paper. Right now, viruses are exploiting that potential to their advantage. But in the future, he says, “we may exploit this to their detriment.”
The new study focused on bacteriophages — viruses that infect bacteria, often referred to as “phages.” The phages in the study can only infect their hosts when bacterial cells have specialized appendages, called pili and flagella, that help bacteria move and mate. The bacteria produce a protein called CtrA that controls the production of these appendages. The new paper shows that several appendage-dependent phages have patterns in their DNA where the CtrA protein can attach, called binding sites. Aryl says that a phage with a binding site for a protein produced by its host is unusual.
Even more surprising, Ariel and the paper’s first author Elia Mascolo, a Ph.D. student in Arrill’s lab, found through detailed genomic analysis that these binding sites were not unique to a phage, or even a group of phages. Many different types of phages had CtrA binding sites – but they all required pili and/or flagella to infect their hosts. It couldn’t be a coincidence, he decided.
The ability to monitor CTRA levels “has been invented several times throughout evolution by different stages of infecting different bacteria,” says Arrill. When distantly related species exhibit a similar trait, this is called convergent evolution – and it indicates that the trait is certainly useful.
Another wrinkle in the story: The first step in which the research team identified CTRA binding sites infects a special group of bacteria known as Caulobacterales. Caulobacterales are a particularly well-studied group of bacteria, as they exist in two forms: a “heaven” form that floats freely, and a “stalk” form that attaches to the surface. The shrub has pili/flagella, and no stalk. In these bacteria, CtrA also regulates the cell cycle, determining whether a cell will divide evenly into two more types of the same type, or asymmetrically to produce a swarm and a stalk cell. will be divided.
Because phages can only infect swarmer cells, it is in their best interest to exit their host when there are many swarmer cells available to infect. Generally, Caulobacterales live in nutrient-poor environments, and they are highly dispersed. “But when they find a good pocket of microhabitat, they become stalked cells and spread out,” says Arrill, eventually producing large amounts of swarming cells.
Therefore, “we hypothesize that phages are monitoring CTRA levels, which go up and down during the life cycle of cells, to detect when a swarmer cell is becoming a stalk cell and a factory of swarmers.” “And at that point, they burst the cell, because there’s going to be a lot of swarm infected around,” says Arrill.
Unfortunately, the method to prove this hypothesis is labor-intensive and extremely difficult, so it was not part of this latest paper – although Eril and colleagues hope to tackle that question in the future. However, the research team does not see any other plausible explanation for the proliferation of CtrA binding sites at several different phages, all of which require pili/flagella to infect their hosts. Even more interesting, they note, are the implications for viruses that infect other organisms — even humans.
“Everything we know about phages, every single evolutionary strategy they have developed, has been shown to translate into viruses that infect plants and animals,” he says. “It’s almost a given. So if phages are listening on their hosts, viruses affecting humans are doing the same.”
There are some other documented examples of phages monitoring their environment in interesting ways, but not so many involving many different phages employing the same strategy against bacterial hosts.
“This new research is the first broad-scope demonstration that phages are listening in terms of what’s happening in the cell, in terms of cell development,” says Arrill. But more examples are on the way, he predicts. At the same time, members of his lab have started looking for receptors for other bacterial regulatory molecules in phages, he says — and they’re looking for them.
The key conclusion from this research is that “the virus is using cellular intel to make decisions,” says Arrill, “and if it’s happening in bacteria, it’s almost certainly happening in plants and animals.” , because if it is an evolutionary strategy that makes sense, evolution will find it and take advantage of it.”
For example, to optimize its strategy for survival and replication, an animal virus may want to know what type of tissue it is in, or how strong the host’s immune response is to its infection. While it can be troubling to think about all the information viruses can collect and possibly use to make us sick, these discoveries also open the way to new treatments.
“If you’re developing an antiviral drug, and you know the virus is listening on a particular signal, maybe you can fool the virus,” says Arrill. Although it is several steps away. For now, “we’re just starting to realize how active the virus is watching us — how they’re monitoring what’s happening around them and making decisions based on that,” says Arrill. . “it’s tempting.”