Researchers from the University of California at San Diego shed light on how the immune system of mammals manages to take advantage of the flaws in viruses to protect itself from their attacks.
- To protect against viral attacks, our immune system produces a protein called NLRP1 which mimics the natural sites through which the virus replicates and infects our body.
To guard against virus attacks, our immune system must be intelligent and particularly reactive to exploit the weaknesses of its attackers.
Constantly on alert to deploy counterattacks to viral infections, the immune system can also sometimes overreact defensively which can lead to tissue damage and autoimmune diseases.
A new study, published in the journal eLife by biologists at the University of California, San Diego, provides a better understanding of the adaptation mechanisms used by cells of the mammalian immune system. Using a multidisciplinary approach that combines bioinformatics, biochemistry and virology, they discovered surprising defensive functions coordinated by a protein called NLRP1, which serves as a sensor for invading pathogens.
NLRP1, “Achilles’ heel” of viruses
The researchers studied viruses from the Picornaviridae family, which generate proteases, enzymes similar to molecular “scissors”, capable of breaking down and activating the NLRP1 protein. Poliovirus, coxsackievirus (responsible for hand disease, foot and mouth disease) and rhinovirus (one of the most common causes of the common cold) are part of the Picornaviridae family.
The analysis revealed that the NLRP1 protein evolved to “sense” these viral proteases which, when they break down NLRP1, trigger an immune response. Interestingly, the NLRP1 protein evolved by mimicking natural sites that the viral protease usually cuts so the virus can replicate. This means that it is difficult for the virus to avoid breaking NLRP1 while maintaining its survivability.
“In our article, we show that the NLRP1 protein acts as a bait for the cleavage of the viral protease and triggers a kind of alarm, or trigger, in the organism, explains Brian Tsu, the lead author of the study. It’s like an Achilles heel for the virus. This allows the host organism to find ways to take advantage of this evolutionarily constrained cleavage.”
An immune trap to exploit in future research
For the authors, this discovery shows that until now we had erroneous ideas about virus-host dynamics. “We often think of viruses taking advantage of the fact that hosts evolve slowly, but we see that hosts have changed that and used the fact that viruses are really stuck here to their advantage, and so they’re using that constraint to activate a immune response”details Matt Daugherty, co-author of the study.
To be able to avoid this trap set by the NLRP1 protein, the viruses analyzed in this study would need to modify many regions of their viral proteases simultaneously, which would be extremely difficult.
While the study was conducted on cells, it also lays the groundwork for potential future applications of this “immune trap”, which could be used in the immune system of the human lungs or brain. “I’m especially excited to research more such cases, as this is an elegant and scalable way to detect and respond to viral infection.”concludes Professor Daugherty.
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