Sunday 17 / November / 2024
California: Inflammasomes are part of a complex network of molecular sensors that our bodies utilise to detect infection. However, immunologists have been intrigued by the processes behind these sensors, which activate responses to dangers such as invading infections.
University of California San Diego researchers disclose a previously undiscovered manner that the immune system recognises some viruses in a new study. CARD8, an inflammasome immune protein, they discovered, may act as a tripwire to identify a variety of viruses, including SARS-Cov-2, which causes COVID-19. Researchers led by Matt Daugherty of the School of Biological Sciences and colleagues from the University of Washington and UC Berkeley discovered that CARD8 acts differently between animals and even amongst people in the human population. The findings, which came from a series of tests involving human cell lines and an examination of CARD8 genetic diversity in mammalian species, were published in the journal PLOS Biology.
"In a version of CARD8, we found that some humans have lost the ability to sense coronavirus infections based on a single genetic difference but have gained the ability to sense viruses in a different family, the enteroviruses--which includes rhinovirus (common cold) and poliovirus," said Daugherty, an associate professor in the Department of Molecular Biology. "So that means it's an evolutionary tradeoff and CARD8 diversity in humans impacts which viruses can be sensed and which ones cannot."
The research team found that the bat version of CARD8 is not able to sense coronaviruses. This could explain how coronaviruses are able to infect bats so easily and become a virus "reservoir."
The findings provide evidence that CARD8 has evolved substantially across different species of mammals and individual humans. According to the authors, "Our findings establish CARD8 as a rapidly evolving, polymorphic, innate immune sensor of positive-sense RNA viruses."
Daugherty said researchers have only found the tip of the iceberg in terms of the way immune sensors sound the alarm about pathogens and infection.
"It's amazing to see this evolutionary balance of one virus to another going from sensing to not sensing--it's mind-blowing," said Daugherty.
More studies are needed to thoroughly determine CARD8's role in the severity of COVID-19 infections and long COVID symptoms.
"It is tempting to speculate that diminished CARD8 inflammasome activation may be a contributing factor to variation in COVID-19 disease outcomes, and more generally for other human pathogenic coronavirus and picornavirus infections," the authors note.
