According to recent findings, viruses ‘decide’ when to remain dormant inside their hosts and when to multiply and burst out, killing the host cell and using information from their environment. Viruses currently take advantage of their ability to observe their surroundings. However, one of the authors warned that “we could exploit it to their detriment in the future.”
According to biological sciences professor and senior author Ivan Erill “ A virus’s capacity to sense its environment including components produced by its host adds “another layer of complexity to the viral-host interaction.” Viruses currently take advantage of that capability for their gain. However, he suggests that “we could exploit it to their detriment in the future.”
The new study concentrated on bacteriophages, also known as “phages” or “viruses that infect bacteria.” The phages in the study can only infect their hosts when the bacterial cells have unique pili and flagella limbs that facilitate movement and reproduction. When these appendages are produced, the bacteria are controlled by a protein called CtrA. The new study demonstrates that many appendage-dependent phages have DNA binding sites or patterns where the CtrA protein can bind. It’s unusual for a phage to have a binding site for a protein made by its host, according to Erill.
Even more astonishingly, through thorough genomic analysis, Erill and the paper’s first author Elia Mascolo, a Ph.D. student in Erill’s lab, discovered that these binding sites were not particular to a single phage or even a specific group of phages. Many different phage types had CtrA binding sites, but to infect their hosts, they all needed pili and flagella. They concluded that it couldn’t be a coincidence.
Various phages that infect various bacteria “have invented the ability to monitor CtrA levels multiple times throughout evolution,” claims Erill. Convergent evolution, which shows a trait is unquestionably beneficial, occurs when distantly related species exhibit a similar trait.
Another twist in the tale is that the Caulobacterales, a particular species of bacteria, are infected by the first phage in which the research team discovered CtrA binding sites.
The Caulobacterales are taken under consideration here because they can take two forms – a “swarmer” form that swims around freely or a “stalked” form that adheres to a surface. The stalks lack pili/flagella, while the swarmers do have them. CtrA controls the cell cycle in these bacteria, determining whether a cell will divide symmetrically to produce one swarmer cell and one stalk cell or asymmetrically to produce two more cells of the same type.
The phages only burst out of their host when plenty of swarmer cells are available to infect because they can only infect swarmer cells. In general, Caulobacterales are widely dispersed and inhabit nutrient-poor environments. However, Erill explains, “when they find a good pocket of microhabitat, they become stalked cells and proliferate, ultimately producing many swarmer cells.”
Therefore, according to Erill, “We hypothesize that the phages are monitoring CtrA levels, which fluctuate throughout the life cycle of the cells, to figure out when the swarmer cell is becoming a stalk cell and becoming a factory of swarmers and at that point, they burst the cell because there will be many swarmers nearby to infect.”
Though Erill and colleagues hope to address that question in the future, the method to prove this hypothesis is labor-intensive and highly challenging, so it wasn’t included in this most recent paper. But since all phages need pili/flagella to infect their hosts, the research team does not see any other possible explanation for the proliferation of CtrA binding sites on so many different phages. They add that the implications for viruses that affect other organisms, including people, are even more intriguing.
He says, “Every single evolutionary strategy that phages have devised, has been shown to translate to viruses that infect plants and animals. It almost seems obvious. Therefore, viruses that infect humans must be doing the same if phages are listening in on their hosts.”
There are a few other instances where phages have been observed to monitor their surroundings in intriguing ways. Still, none involve numerous phages using the same tactic to attack numerous bacterial hosts.
According to Erill, this latest study is “the first comprehensive demonstration that phages are listening in on what’s going on in the cell, in this case, in terms of cell development.” But he anticipates that there will be more instances. He claims that members of his lab have already begun searching for receptors for additional bacterial regulatory molecules in phages and that they are succeeding in doing so.
The most important lesson to be learned from this research is that “the virus is using cellular intel to make decisions,” according to Erill. If it’s happening in bacteria, it’s almost certainly happening in plants and animals because evolution will find and use any sensible evolutionary strategy.
An animal virus might be interested in knowing the type of tissue it is in or the strength of the host’s immune response to tailor its strategy for survival and replication. Though it may be unsettling to consider all the data viruses could amass and potentially use to make us sicker, these discoveries also provide opportunities for novel treatments.
“Maybe you can fool the virus,” says Erill, “If you are developing an antiviral drug and you know the virus is listening in on a specific signal.” But that’s a reasonable distance away. Bill says that at the moment, “We are just starting to realize how actively viruses have eyes on us — how they are monitoring what’s going on around them and making decisions based on that. It’s intriguing.