News – Scientists open new windows to understand more about the evolutionary arms race between viruses and the hosts they are trying to infect. Chess organisms and pathogens are in a permanent chess game to take advantage of each other’s weaknesses.
Such research holds a tantalizing cry for human health as the immune system increasingly warns to take measures against new viral attacks. But opening too much immune response can damage and infect you.
New study published in the journal eLife with biologists at the University of California San Diego has revealed insights into the complex, changing mechanisms in the immune system employed by cells of mammalian immune systems. Through a multidisciplinary approach that combined bioinformatics, biochemistry and virology, Biological Sciences graduate students Brian Tsu, Chris Beierschmitt and Andy Ryan, Associate Professor Matt Daugherty and their colleagues at UC Berkeley discovered remarkable protective actions coordinated with a protein called NLRP1, which serves as its sensor for invasive pathogens.
The study was in progress Picornaviridae family viruses, which generate proteases, or “molecular scissors” that can cleanse and activate NLRP1. These viruses include human pathogens such as poliovirus, coxsackievirus (responsible for hand, foot and mouth disease) and rhinovirus (one of the most common causes of the common cold). The analysis showed that NLRP1 has recently evolved to “sensitize” these viral proteases through a type of trap that stops an immune response in response to being cut off by the viral proteases. Interestingly, NLRP1 has evolved to do so by mimicking natural sites that normally require the cutting of the viral protease in order for the virus to reproduce, making it difficult for the virus to reproduce. virus avoids NLRP1 while maintaining its ability to survive.
“In our paper we show that NLRP1 works by activating viral protease activity and removing a type of warning device, or tripwire, in the organism,” said Tsu, lead author of the inspection. “This is similar to Achilles heel virus. This will allow the organism to develop ways to take advantage of this severely constrained condition. ”
Daugherty said the results offer an interesting reversal of conventional beliefs about the dynamics of virus hosting.
“We often think of viruses taking advantage of that hosting gradual evolution, but we see that the guests have turned the tables and used the viruses are really here to their advantage, so there is they use this restriction to trigger an immune response. ”
Although evolution is often thought to occur one step after another, the viruses examined in this study would have to modify several regions within their viral proteins in order to evolve. around the tripwire protection, which would be extremely difficult.
The research was carried out in cells but lays the foundation for possible future clinical applications in which the tripwire action could be used in immune suppression in human systems. such as the lungs, brain and other areas. Based on the results of the study in individual cells, new research avenues are opening up to study how the tripwire works across whole organisms.
“I’m really excited to be looking for more of these issues because this is a very elegant way to detect and respond to a viral infection,” Daugherty said.
The full list of authors includes: Brian Tsu, Christopher Beierschmitt, Andrew Ryan, Rimjhim Agarwal, Patrick Mitchell and Matt Daugherty.
The research was funded by the National Institutes of Health (R35 GM133633), Pew Biomedical Scholars Program, Hellman Fellows Program, graduate research fellowship of the National Science Foundation (2019284620) and Jane Coffin Childs Memorial Fund for postdoctoral fellowship of Medical Research.