Just as pathogens evolve new tricks to evade our body’s safeguards and cause infection, our immune system can also develop new tricks that keep these nasty invaders at bay. New research has revealed an interesting example of this, demonstrating how the mammalian immune system deploys a type of tripwire defense to fend off viral attacks.
The research was carried out by biologists at the University of California San Diego, who pitted cells from the mammalian immune system against the Picornaviridae family of viruses. These include common foes like rhinovirus, poliovirus and the coxsackievirus (the pathogen behind hand, foot and mouth disease) and work by activating a protein called NLRP1 that drives potent inflammation in the host.
As part of this process, viruses generate enzymes that act as molecular scissors to snip portions of the protein, which they then use to take hold, replicate and spread throughout the host. But through its analysis, the team discovered that the NLRP1 protein has recently evolved some useful new capabilities.
The protein is able to effectively set traps for the pathogens, mimicking the component that they usually cut away as they invade the host. The cutting of this “tripwire” has the effect of triggering an immune response to the pathogens, which helps swing the battle back in favor of the host.
“In our paper we’re showing that NLRP1 acts to bait viral protease cleavage and set off a sort of alarm, or tripwire, in the organism,” said Brian Tsu, the lead author of the study. “This is like an Achilles heel to the virus. This allows the host organism to evolve ways to take advantage of this evolutionarily constrained cleavage.”
In terms of what this could mean for clinical applications, the scientists imagine this mechanism one day being leveraged to fend off viral infections in the lungs, brain or other parts of the body. Such feats are a long way off, but in the meantime, the discovery offers fascinating new insights into the way immune systems can evolve.
“We often think of viruses taking advantage of the fact that hosts evolve slowly, but we’re seeing that the hosts have turned the tables and used the fact that the viruses are really stuck here to their advantage, and therefore they use this constraint to activate an immune response,” says study author Matt Daugherty.
The research was published in the journal eLife.
